|
|
|
|
God’s
Organism? The chick as a model system for memory studies
|
|
Steven P R Rose
Brain
and Behaviour Research Group,
The
Open University, Milton Keynes MK7 6AA, UK
Email:s.p.r.rose@open.ac.uk
Learn.
Mem. 2000 7: 1-17.
With thanks to Learning
and Memory for permission to reproduce this review.
|
|
|
|
|
|
|
|
|
|
|
| |
|
|
|
|
|
CONTENTS
The
young chick is a powerful model system in which to study the biochemical
and morphological processes underlying memory formation. Training
chicks on a one trial passive avoidance task results in a molecular
cascade in a specific brain region, the intermediate medial hyperstriatum
ventrale. This cascades is initiated by glutamate release and
engages a series of synaptic transients including increased calcium
flux, upregulation of NMDA-glutamate receptors, membrane protein
phosphorylations and the retrograde messenger NO. Expression of
immediate early genes c-fos and c-jun precedes the synthesis,
glycosylation and redistribution, 4+ hours downstream, of a number
of synaptic membrane proteins, notably NCAM and L1. Other membrane
proteins required in the early phase of memory formation include
the amyloid precursor protein APP and Apolipoprotein E. There
are concomitant increases in dendritic spine number and changes
in synaptic structure. Non-synaptic factors including corticosterone
and BDNF can modulate retention of the avoidance response, enhancing
the salience of otherwise weakly retained memory. These results
are discussed in relation to general concepts of memory formation
and the spatio-temporal distribution of the putative memory trace.
|
|
| |
|
Early learning in the chick
|
|
|
CONTENTS
The
distinguished biochemist Hans Krebs once remarked that God had
provided just the right organism with which to study any particular
biological problem. The purpose of this review is to argue that
the young domestic chick rates high amongst God’s organisms
for the study of the molecular and cellular mechanisms of memory
formation. Chicks are precocial birds, and need actively to explore
and learn about their environment from the moment they hatch.
Thus they learn very rapidly to identify their mother on the basis
of visual, olfactory and auditory cues (imprinting), to distinguish
edible from inedible or distasteful food, and to navigate complex
routes. Training paradigms that exploit these species-specific
tasks work with the grain of the animal’s biology, and because
such learning is a significant event in the young chick’s
life the experiences involved may be expected to result in readily
measurable brain changes. Chicks have large and well-developed
brains and soft unossified skulls, making localised cerebral injections
of drugs easy without the use of implanted cannulae or anaesthesia.
The virtual lack of any blood-brain barrier in these young animals
also ensures rapid entry into the brain of peripherally injected
agents. Against these advantages must be weighed the relatively
limited knowledge of the intimate neuroanatomy of the avian brain
(but see Csillag, 1999), a degree of genetic heterogeneity, and
the complication resulting from the fact that in such young animals
task-induced changes in cerebral biochemistry, electrophysiology
or morphology are superimposed on rapidly developing neural systems
(Andrew, 1991; Rogers, 1995).
|
|
| |
|
|
|
|
|
CONTENTS
The
study of both the phenomenology and the neurobiology of learning
and memory in avian species has a long and distinguished history.
Pigeons vied with rats as the favourite laboratory animals for
behaviourists studying conditioning, but more ‘natural’
forms of learning have long fascinated. Marler, Konishi and Notttebohm
pioneered the behavioural and neurobiological analysis of song
learning in song sparrows, canaries and zebra finches (Marler,
1991;Konishi, 1989;Nottebohm, 1970; 1980), tracing neural pathways,
identifying issues of lateralisation, hormonal and related effects
which have found their parallels in work with the chick. Krebs,
Sherry and their colleagues explored the role of the hippocampus
in food-storing birds such as marsh tits and chickadees (Krebs,
Sherry, Healy, Perry and Vaccarino, 1989). Some of this work has
more recently begun to move to the biochemical and molecular level
that I focus on here in the context of the chick. The prospect
of using the young chick for the study of cellular and molecular
memory mechanisms emerged in the 1960s. Bateson and his colleagues
opted for the study of visual imprinting (for review see Horn,
1985). Imprinting, as a form of early learning in some avian species,
had been known folklorically for many years (Bateson, 1966), but
was drawn to scientific attention by the work of Lorenz (eg Lorenz,
1935) although his interpretations of the phenomenon were not
uncritically received. The study of the neurobiology of imprinting
has continued in Horn’s and other labs (McCabe and Nicol,
1999; Johnston and Rogers, 1998). Scheich, Braun and their colleagues
explored auditory imprinting (Scheich, 1987; Braun, Bock, Metzger,
Jiang and Schnabel, 1999). In these models, chicks are exposed
for up to two hours to visual or auditory cues that come to represent
‘mother’ (flashing light, stuffed hen, tone). They will
subsequently approach the familiar object when offered a choice
between it and an unfamiliar stimulus.
Cherkin
(1969) developed a one-trial passive avoidance learning task based
on the young chick’s tendency to peck at small bright objects
such as beads, discussed in more detail below. In an appetitive
visual discrimination task the chick learns to distinguish food
crumbs scattered on the floor of its pen from rather similar pebbles
or beads glued to the surface (Andrew and Rogers, 1972; Tiunova,
Anokhin and Rose, 1998). Isolated chicks will quickly learn a
simple maze in order to rejoin their hatchmates (Gilbert, Patterson
and Rose, 1989; Regolin and Rose, 1999). Barber et al (Barber
A, Gilbert and Rose, 1989; Barber TA, Howorth, Klunk and Cho,
1999) have employed a sickness-aversion protocol in which chicks,
having pecked a neutral object (a dry coloured bead) and subsequently
been made sick by intraperitoneal injection of lithium chloride,
will later avoid the bead. Social learning, in which one chick
observes and learns from the experience of a second is another
important paradigm, bypassing as it does direct physiological
or pharmacological manipulation of the learner (Johnston, Burne
and Rose, 1999). Bradley and his colleagues (Bradley, Burns, King
and Webb, 1999) have explored forms of LTP in the chick forebrain
which correlate with the training protocols described below. However
this review is largely confined to the data from the passive avoidance
model.
The
passive avoidance task has the merits of being rapid and sharply
timed (chicks peck a bead within 10 seconds) and as many as 60
chicks can be trained in a single session. In the standard version
of the task in our lab, day-old chicks are held in pairs in small
pens, pretrained by being offered a small dry white bead, and
those that peck trained with a larger (4mm dia) chrome or coloured
bead coated with the distasteful methylanthranilate (MeA) (Lossner
and Rose, 1983). Chicks that peck such a bead show a disgust reaction
(backing away, shaking their heads and wiping their bills) and
will avoid a similar but dry bead for at least 48hr subsequently.
However, they continue to discriminate, as shown by pecking at
control beads of other colours. Chicks trained on the bitter bead
are matched with controls which have pecked at a water-coated
or dry bead, and which peck the dry bead on test. Generally some
80% of chicks in any hatch group can be successfully trained and
tested on this protocol. Each chick is usually trained and tested
only once. These protocols, coupled with close observation of
the chicks, enables one to distinguish the general effects of
the training experience with its accompanying visual, motor and
gustatory engagements, from the cellular processes involved necessarily
and specifically in memory formation for the task (eg Rose and
Harding, 1984). This distinction is reflected in the data presented
below. Other labs (see Andrew, 1991 for review) slightly vary
the protocols in ways which may affect the temporal sequence of
post-training behavioural and molecular processes (Burne and Rose,
1997). Nonetheless, where data is comparable, there is broad consensus
concerning both the behavioural and biochemical sequelae of training
amongst the several chick labs.
Both
correlative and interventive strategies are possible. In the correlative
approach, appropriate brain regions can be dissected from trained
and control birds at specific post-training times and tissue processed
for biochemical, immunocytochemical, autoradiographic or microscopic
analysis. It is also possible to prepare tissue slices (prisms)
or synaptoneurosomes from the chicks, enabling calcium and neurotransmitter
fluxes to be determined. Braun’s group (Gruss and Braun,
1996; Daisley, Gruss, Rose and Braun, 1998) has developed a microdialysis
system enabling such fluxes to be measured in vivo during
both training and testing. In the interventive approach all the
birds are trained on MeA, and injected either before or after
training with drug, antibody or antisense, or vehicle, to explore
the possible enhancing or amnestic effect of the agent. Chicks
that peck the previously distasteful bead on test are considered
to be amnesic for the training. As this pecking response requires
a positive and accurate act by the bird, it also controls for
effects of the agent on attentional, visual and motor processes.
The
sharply timed nature of the learning experience, together with
a combination of these experimental strategies, has enabled us
to identify a biochemical cascade associated with memory consolidation
in the minutes to hours following training. Thus a change in some
biochemical marker at a specific post-training time, occurring
in trained compared with control chicks, might imply its direct
engagement in memory expression at that time. Alternatively it
could indicate the mobilisation of that marker as part of a sequence
leading to the synthesis of a molecule, or cellular reorganisation,
required for expression of memory. A similar argument applies
to the timing of the onset of amnesia following intracerebral
drug injection.
|
|
| |
|
|
|
|
|
CONTENTS
2-deoxyglucose
studies revealed that two regions of the chick forebrain show
enhanced metabolic activity in the forty minutes following training
(Kossut and Rose 1984). These are the intermediate medial hyperstriatum
ventrale (IMHV), an association ‘cortical’ area previously
implicated in visual imprinting (Horn, 1985), and the lobus parolfactorius,
a basal ganglia homologue (Csillag, 1999). The chick brain is
strongly lateralised (Andrew, 1999: Rogers and Deng, 1999) and
many, though not all of the molecular events we have observed
are confined to the left IMHV. It is this cascade, primarily as
identified by our lab, which forms the focus of the present review,
although this means that it is not possible to do full justice
to the work of the La Trobe group of Ng and his colleagues which
most closely parallels our own (for reviews see Gibbs and Ng,
1977; Ng and Gibbs, 1991; Gibbs, Ng and Crowe, 1991 and other
references in this text, passim). The combination of correlative
and interventive methods has enabled an approximate temporal sequence
to be traced. Table 1 shows the effects of injecting specific
interventive agents just prior to or just following training and
the time of onset of amnesia consequent on that injection. The
cartoon of Fig 1 interprets these and the correlative and enhancement
data discussed below in terms of a temporal sequence of molecular
events in the IMHV following the bead peck.
Time
of onset of amnesia for the passive avoidance task
following injection of blocking agents just before or after
training.
|
Agent
|
Process
Blocked
|
Onset
of Amnesia
(min)
|
| 1)
Muscimol |
GABA
agonist
|
10-15
|
| 2)
Nitroarginine |
NO
synthesis
|
15-30
|
3)
TFP; W13; A3;
W9;HA1004 |
Ca2+/CAM
kinase/B50?
|
15-30
|
| 4)
w-conotoxin GVIA |
N-type
Ca2+ channels
|
15-30
|
| 5)
2-D-galactose* |
Glycosylation
|
30-40
|
| 6)
Anti-L1* |
Signal
transduction
|
30-40
|
7)
H7; HA156;
H8; H9; ML9 |
PKA,
PKC, PKG, B50
neurogranin phosphorylation
|
60
|
| 8)
c-fos antisense |
c-fos
expression
|
60
|
| 9)
b-APP antisense |
b-APP
expression
|
60
|
| 10)
Anisomycin* |
Protein
synthesis
|
60
|
| 11)
NDGA |
Arachidonic
acid synthesis
|
75
|
| 12)
AP5; MK-801 |
NMDA
receptors
|
90
|
| 13)
Dantrolene |
Intracellular
Ca2+ stores
|
60-180
|
| 14)
RU 38486 |
Glucocorticoid
receptors
|
60-180
|
| 15)
anti-BDNF |
BDNF
|
60-180
|
Notes
*Anisomycin
is also amnestic if injected 4hr post-training; anti-L1 and 2-D-gal
if injected at 5.5 hr post-training. Agents only effective during
the ‘second wave’ discussed in the text are not listed
here.
References
to Table 1
-
Clements
and Bourne, 1996
-
Holscher
and Rose, 1993
-
Serrano
et al 1994
-
Clements,
Rose and Tiunova, 1995
-
Crowe
et al, 1994
-
Scholey
et al, 1995
-
Serrano
et al, 1994
-
Mileusnic
et al, 1996
-
Mileusnic
et al, 1999
-
Freeman
and Rose, 1995
-
Holscher
and Rose, 1994
-
Rickard,
Poot, Gibbs, and Ng,1994
-
Salinska
et al, 1999b
-
Sandi
and Rose, 1994b
-
Johnston
et al, 1999
|
|
|
|
|
|
The first hour
|
|
|
CONTENTS
During
training, and in the five minutes which follow, there is enhanced
release of glutamate in the IMHV, detected both by microdialysis
in vivo (Daisley et al, 1999), and in tissue slices (Daisley
and Rose, 1994). Over the same time period there is also an increase
in potassium -stimulated calcium concentration in synaptoneurosomes
isolated from the IMHV (Salinska, Chaudhury, Bourne and Rose,
1999). Within the succeeding forty minutes, although we cannot
assign them a precise temporal dependency, we have found: increases
in NMDA-stimulated calcium flux in synaptoneurosomes (Salinska
et al, 1999); in ligand binding to the NMDA-glutamate receptor
(Stewart, Bourne and Steele, 1992; Steele, Stewart and Rose, 1995)
and of phosphorylation of the presynaptic membrane protein B50
(aka GAP43), (Ali, Bullock and Rose, 1988) coupled with a translocation
of cytosolic PKC to the membrane (Burchuladze, Potter and Rose,
1990). There is increased release of the putative retrograde messenger
arachidonic acid, in tissue prisms prepared 30-75min post-training,
though the onset time for amnesia if the arachidonic acid synthesis
is blocked with phospholipase A2 inhibitors is delayed
until 75 minutes (Clements and Rose, 1996; Holscher and Rose,
1994). Interventive studies with MK801 (Burchuladze and Rose,
1992), the N-type calcium channel blocker W-conotoxin GVIA (Clements,
Rose and Tiunova, 1995) and PKC inhibitors such as mellitin and
H7 (Burchuladze et al, 1990), injected into the IMHV either just
before or just after training, all produce amnesia with an onset
time of 30min to an hour. GABAA agonists are also amnestic
at this time (Clements and Bourne, 1996); so too is nitroarginine,
which blocks synthesis of the putative retrograde messenger NO
(Holscher and Rose, 1993; Rickard, Ng and Gibbs, 1998). Other
labs have found an involvement of a variety of protein kinases,
notably PKA, over this period (Serrano, Rodriguez, Bennett and
Rosenzweig, 1995).
Most
of these processes have been observed in other learning paradigms
in mammals, and are also reminiscent of the sequence identified
in the induction phase of NMDA-dependent LTP (Izquierdo and Medina,
1997). (An exception is our failure to observe any effect on retention
of blocking post-synaptic L-type calcium channels with nimodipine.
The N-type calcium channels blocked by conotoxin are generally
assumed to be presynaptic in mammals, although this needs to be
confirmed in the chick.) However, the merits of the brevity of
the training experience in the chick and the fairly sharply timed
onset of amnesia following various pharmacological interventions
do make it possible to propose a rather more precise sequence
for the various steps in the cascade than is otherwise feasible.
As indicated in Fig 1 the observations also cast some light on
the long-running discussion of pre versus post-synaptic events
in the initiation of LTP (Bliss and Collingridge, 1993). Thus
NMDA upregulation is temporally downstream of the initial in
vivo increases in glutamate release and in vitro increases
in potassium stimulated calcium flux. These early events, together
with the changes in phosphorylation of the presynaptic B50/GAP
43, and, if taken at face value, the conotoxin data, all point
to presynaptic engagement. The amnesia resulting from blocking
NOS with nitroarginine, which sets in by thirty minutes, implies
two-way signalling between post and pre-synaptic sides, and that
this continued traffic is necessary if both are to undergo reconstruction
during the later stages of memory formation.
Thus
it would appear that the training experience generates a sequence
of rapid synaptic transients which provide a temporary ‘hold’
for the memory — the phases categorised as short and intermediate
term memory by Gibbs and Ng (1977; see also Patterson, Alvarado,
Rosenzweig and Bennett, 1988). As well as forming the brain substrate
of the remembered avoidance over this period, these transients
must serve two other functions. They must initiate the sequence
of pre- and post-synaptic intracellular processes which will in
due course result in the lasting 'synaptic' changes presumed to
underlie long term memory, and they must also serve to ‘tag’
relevant active synapses, perhaps via B50 and other membrane phosphorylations
so as to indicate those synapses later to be more lastingly modified.
|
|
| |
|
|
|
|
|
CONTENTS
A
key step in the intracellular cascade must be the link between
synapse and nucleus. Calcium is clearly a major player here, and
that intracellular calcium signalling may be important is indicated
by our recent observation that within 10 min post-training there
is also a mobilisation of synaptoneurosomal ryanodine-sensitive
calcium stores (Salinska, Bourne and Rose, 1999), whilst dantrolene,
which blocks calcium release from these stores, injected 30 min
pre- or 30 min post-training, produces amnesia by 3hr post-training.
Synaptoneurosomes are largely presynaptic, though they contain
resealed postsynaptic (dendritic) elements as well, so it is not
possible to distinguish whether the mobilised calcium stores are
located at one, the other or both sides of the cleft.
That
activation of a number of transcription factors must be amongst
the next steps in the process is clear from the elucidation of
a role for CREB in several mammalian learning paradigms.We however
have focused on the role of immediate early genes, c-fos and c-jun.
That visual stimulation alone is sufficient to activate fos or
jun expression is well known, as it was not surprising that we
found that passive avoidance training elicited such activation
(Anokhin, Mileusnic, Shamakhina and Rose, 1991). To control for
the specificity of the expression we compared overtrained and
undertrained chicks on the pebble floor task described above.
Although both groups showed the pecking behaviour, the learning,
as opposed to the already trained group, showed a clear increase
in jun expression (Anokhin and Rose, 1991).Further evidence as
to the necessity of fos expression for longer term memory is provided
by the observation that antisense to c-fos, given 6 or more hours
pretraining, blocks its synthesis (Mileusnic, Anokhin and Rose,
1996) and chicks become amnesic within 3hr post-training.
One
of the few universal findings in studies of biochemical processes
in memory formation is that long(er) -term memory is protein synthesis
dependent (Davies and Squire, 1984). Passive avoidance training
is no exception, and anisomycin injected into the IMHV either
before or up to some 60 minutes post-training results in amnesia
for the avoidance. If the anisomycin is injected before training,
amnesia sets in by the end of the first post-training hour, leading
to the suggestion that beyond this period memory is protein-synthesis
independent (Gibbs and Ng, 1977). However, the earlier view that
beyond this time a protein synthesis-independent, long-term memory
has been established is no longer tenable. Whilst anisomycin injections
2 and 3 hr post-training are without effect on memory, injections
given 4 or 5 hrs post-training are amnestic in animals tested
at 24 hr (Freeman and Rose, 1995) as earlier found for rats by
Grecksch and Matthies (1980). Thus there is a second, downstream
wave of training-related protein synthesis that we interpret as
being the period during which late genes are activated and structural
proteins synthesised. However, this is not the entire explanation;
other processes are also mobilised during this later time period.
Whereas 30 minutes post-training NMDA but not AMPA receptors are
engaged, 5.5 hr post-training AMPA but not NMDA receptors are
upregulated, leading to an increase in AMPA-stimulated calcium
flux in synaptoneurosomes. CNQX given at this time is amnestic
(Steele and Stewart, 1995; Salinska et al, 1999). The relationship
between these events and the protein synthetic wave is still not
clear.
Whilst
much attention within the learning and memory community is currently
directed towards the roles of the many transcription factors involved
in the early phases of memory formation, we have focussed on identifying
the later gene products. There is considerable evidence for a
role for synaptic membrane glycoproteins (Popov, Schulzeck, Pohle,
and Matthies,1981, for reviews see Matthies, 1989; Rose, 1995a,b).
Amongst the membrane glycoproteins are a variety of receptors,
and the family of cell and matrix adherence molecules. The cell
adhesion molecules (CAMs) are transmembrane molecules, whose glycosylated
extracellular domains can bind either homophilically or heterophilically,
providing a mechanism for associating pre- and post-synaptic membranes.Their
potential role in synaptic plasticity has long been emphasised
by Edelman (1985) (see also Pollerberg, Sadoul, Goridis and Schachner,
1985; Goelet, Castelluci, Schachner and Kandel, 1986). NCAM in
particular exists in a number of isoforms. In its immature form
is relatively highly sialylated, and less adherent. The mature
form is desialylated, and more adherent. This has led to the suggestion,
for which there is now good empirical evidence (Doyle, Nolan,
Bell, and Regan, 1992a) that synaptic restructuring, either in
the context of general development, or more specifically as a
result of training experiences, requires first a sialylating,
deadherence step, enabling synaptic mobility to occur, and subsequently
desialylation and readherence. However these are not the only
roles proposed for the CAMs; they are also likely to be involved
in transmembrane signalling.
Fucose
is a general glycoprotein precursor, and training chicks on MeA
results in a long-lasting increased fucosylation of synaptic membrane
glycoproteins. The use of the competitive inhibitor of galactose
incorporation into glycoproteins, 2-deoxygalactose (2-d-gal),
which prevents terminal fucosylation was pioneered by Matthies
and his colleagues. Injected into the IMHV either around the time
of training, or 6-8hr later, 2-d-gal results in amnesia in chicks
tested at 24hr (Rose and Jork, 1987; Scholey, Rose, Zamani, Bock,
and Schachner, 1993). This suggests a double wave of glycoprotein
synthesis analogous to that already found with anisomycin, and
comparable to that observed by the Matthies group following a
brightness discrimination task in rats. These time windows are
displaced with respect to the effects of anisomycin, occurring
prior to anisomycin-induced amnesia at the first time point, and
after it at the second (Freeman and Rose, 1995; Crowe, Zhao, Sedman
and Ng, 1994). We interpret this as indicating that during the
first period 2-d-gal is blocking post-translational glycosylation
of already synthesized proteins, whilst at the second time period
it affects de novo glycoprotein synthesis.
Among
the glycoproteins whose synthesis is blocked by 2-d-gal are a
number of CAMs. Two in particular are required for longer term
memory; NCAM and NgCAM (aka L1) (Scholey et al,1993; Scholey,
Mileusnic, Schachner, and Rose,1995). Both have also been shown
to be required for maintenance of LTP (Luthi, Laurent, Figurov,
Muller, and Schachner,1994). NCAM levels also increase after visual
imprinting (Solomonia, McCabe and Horn, 1995). Training chicks
on MeA results in a redistribution of NCAM within the synaptic
junction, as detected by immunogold labelling (Rusakov, Davies,
Krivko, Stewart and Schachner, 1994; Skibo, Davies, Rusakov, Stewart
and Schachner, 1993). Specific blocking of NCAM synthesis with
antisense, injected over the 24hr post-hatch period before the
birds are trained, does not prevent the chicks learning the avoidance,
but amnesia sets in within 3hr (Mileusnic, Lancashire and Rose,
1999). However, interference with the functioning of already synthesised
CAM molecules is also amnestic. Thus if antibodies which bind
to the extracellular domains of either NCAM or L1 are injected
into the IMHV at 5-6hr post-training, chicks show amnesia when
tested at 24hr (Scholey et al, 1993; 1995), a time at which the
antibodies themselves are no longer detectable in the brain. Antibodies
to NCAM are not amnestic if injected at other times, but antibodies
to L1, injected 30 min pretraining, are also amnestic when the
chicks are tested at 24hr. The extracellular domains of L1 include
fibronectin and immunoglobulin regions, and using recombinant
fragments to these regions we found that blocking the immunoglobulin
domain at —30min, but not at +5.5hr, resulted in amnesia,
while by contrast blocking the fibronectin domain at +5.5hr but
not at —30min was amnestic (Scholey et al 1995). This biochemical
version of a double dissociation experiment led us to postulate
that it was the cell signalling function of L1, mediated via the
immunoglobulin domain, which was engaged in the early phases of
memory formation, whilst the fibronectin domains of NCAM and L1
were required in the deadherence/ readherence processes at the
later time point. It is presumably at this time, 5-8hr downstream
of the training event, whilst their epitopes on the external domains
are open to attack, that antibody binding can occur and hence
amnesia result.
Somewhat
to our surprise, we have recently found that antibodies to two
other transmembrane proteins also produce amnesia if injected
30 min pretraining, but not at later times. These are the lipid
trafficking protein ApoE, and the cell-matrix adherent amyloid
precursor protein, APP (Lancashire, Mileusnic and Rose, 1998;
Mileusnic, Lancashire, Johnston and Rose, 1999). These effects
may not be mutually independent, as there is evidence for interaction
between APP and ApoE (Huber, Martin, Lofler and Moreau, 1993;
Lancashire et al, 1998)and both may be involved in the transmembrane
signalling processes that we have argued are required in the early
stages of memory formation. As both proteins are implicated in
Alzheimer’s disease, further elucidation of their mode of
action in normal memory formation may provide clues as to the
memory impairment characteristic of that condition.
|
|
| |
|
|
|
|
|
CONTENTS
The
longer-term consequence of this cascade is thus the modification
of synaptic connectivity, detectable biochemically in terms of
changes in the configuration and distribution of NCAM, amongst
other synaptic markers. The presumed end point for memory storage
is modulation of synaptic connectivity, by altering synaptic number,
and/or relocating or structurally modifying existing synapses
and dendritic spines. Such changes have been observed in a variety
of paradigms, from enriched and impoverished environments to LTP
and memory formation (Chang and Greenough, 1984: Bailey and Kandel,
1993). Might the biochemical changes we have observed in the chick
IMHV following passive avoidance training also result in changes
in synaptic morphology, detected by quantitative microscopy? In
a series of studies, Stewart and his colleagues have been able
to show changes in both pre- and post-synaptic elements. Thus
24hr post training there is increased dendritic spine density
in projection neurons of the IMHV (Patel, Rose and Stewart, 1988),
and at the same time changes in the numbers and dimensions of
synaptic junctions, presynaptic boutons and synaptic vesicle number
in both IMHV and lobus parolfactorius. These findings must however
be contrasted with the observation by the Magdeburg group that,
seven days following acoustic imprinting, there in a sharp decrease
in spine number in the relevant forebrain region.(Wallhauser and
Scheich, 1987). These results might be reconciled if we envisage
that following training there is an initial efflorescence of spines,
followed by a subsequent pruning, as argued, for instance, by
Edelman (1985); but see Purves (1988). The increases in synapse
number at 24hr found by Stewart are protein-synthesis dependent.
However there are also transient changes in number detectable
with an hour post training in the right IMHV, which may be attributable
to synapse splitting rather than de novo synapse production
(For reviews of these morphological changes see Stewart and Rusakov,
1995; Rose and Stewart, 1999).
|
|
| |
|
Factors affecting the salience of memory
|
|
|
CONTENTS
Having
pecked a bead coated in MeA, chicks avoid a similar but dry bead
for at least 24hr subsequently. However, if the aversant is made
less strong, by for instance using a 10% solution of MeA in alcohol,
the birds peck and display a disgust reaction, but will avoid
similar beads for only 6-9hr subsequently (Sandi and Rose 1994a;
see also Burne and Rose, 1997). Although insofar as we have compared
them, weak training initiates a similar set of synaptic transients
to those produced in the strong version of the task, these are
apparently not sufficient to result in gene expression, as glycoprotein
synthesis does not occur. Our assumption is that the temporal
relationship between the fading of the memory trace for the weak
training beyond 6hr and the wave of glycoprotein synthesis that
occurs at this time with strong training is not fortuitous (Rose,
1995b). However, there are a variety of factors which can affect
the salience of this ‘weak learning’ experience, which
result in memory being retained as for the strong learning.
Chicks
are normally held in their pens in pairs, as this diminishes stress.
If they are trained on 10% MeA, and then separated, stress levels
increase, and retention persists for 24hr (Johnston and Rose,
1998). The normal training procedure is indeed stressful, as is
shown by the fact that 5-10min following training chicks on the
strong but not the weak version of the task there is an increase
in plasma corticosterone levels (Sandi and Rose, 1997a). Further
if corticosterone is injected into the IMHV just before or just
after weak training, retention is also enhanced (Sandi and Rose,
1994a). The enhancing effects of stress can be blocked by injection
of antagonists of glucocorticoid receptors into the IMHV, which
is rich in such receptors. Blockade of these receptors is also
amnestic for strong training (Sandi and Rose, 1994b), as is inhibition
of peripheral corticosterone synthesis with metyrapone or aminoglutethimide
(Loscertales, Rose and Sandi, 1997). Corticosterone has effects
both at the membrane and genomically and it is relevant that we
have shown that, independently of training, injections of corticosterone
into the IMHV will enhance glycoprotein synthesis 6hr subsequently
(Sandi, Rose, Mileusnic and Lancashire, 1995; Sandi and Rose,
1997b). As might be anticipated the effects of corticosterone
are dose-dependent in the classic inverted-U form. 1µg injected
prior to weak training enhances retention, whilst higher doses
do not, 1-5µg injected prior to strong training diminishes
retention.(Sandi and Rose, 1997a).
Neurotrophins
also affect the salience of weak training. Recombinant brain-derived
neurotrophic factor (BDNF), but not NGF or NT-3, injected just
before or just after weak training, will enhance 24hr retention.
Reciprocally, antibodies to BDNF are amnestic for strong training,
amnesia setting in within 3hr (Johnston, Clements, and Rose, 1999).
How BDNF may exert its effect is not clear. There are suggestions
that it may act as a retrograde messenger, that it generates an
intracellular signalling cascade via TrkB receptors, and that,
like corticosterone, it may interact with GABAergic systems (see
McKay, Purcell and Carew, 1999 for review). In this respect the
fact that just as GABA agonists are amnestic for strong training,
so antagonists enhance weak training (Clements and Bourne, 1996)
may be significant.
These
findings are of both theoretical and practical relevance. First,
they remind us that although, especially under the influence of
the neurophysiological observations of synaptic interactions during
LTP, cellular theories of memory formation are heavily based on
Hebbian models, memory is not just a pre/post synaptic event.
Rather, whether any particular experience is learned or not depends
on a much wider array of neural and peripheral factors, humoral
and perhaps also immunological (see McGaugh, 1989, Damasio, 1994).
The entire animal is thus involved in any learning experience.
Second, together with the observations on ApoE and APP described
in the previous section, they may point the way towards developing
effective agents for therapeutic intervention in conditions of
memory deficit.
|
|
| |
|
|
|
|
|
CONTENTS
This
review has focussed on the sequence of biochemical events occurring
in the chick IMHV consequent on passive avoidance training, and
I have argued that the cascade we have identified, leading as
it does to measurable morphological changes in synaptic connectivity,
is a necessary part of memory consolidation. Does this however
mean that the IMHV contains some lasting representation of the
association between bead and bitter taste, the elusive engram?
A combination of electrophysiological and lesioning experiments
which have been conducted in parallel with those described here,
but are outside the remit of this review, makes clear that this
is not simply the case (For review, Rose, 1999). Within the hours
following training, biochemical changes occur in other brain regions
than the left IMHV including the right IMHV and lobus parolfactorius,
and the memory trace, if such it is, becomes both fragmented and
redistributed. The IMHV seems to retain some aspects of the memory
including a colour discrimination, whilst others, related perhaps
to the size and shape of the bead, may be located to the lobus
parolfactorius (Patterson and Rose 1992; Barber et al.1999). Again
this points to the conclusion that learning and memory formation
and retention engage not simply a discrete neuronal ensemble
in a small brain region, but a much wider set of spatially and
temporally dynamic processes, linked and given coherence by some
form of binding mechanism (Freeman, 1999; Singer, 2000).
|
|
| |
|
|
|
|
|
CONTENTS
I
have argued that the chick may be at least one of God’s organisms
for the study of the molecular processes of memory formation,
but it is important to address the question of whether the processes
we have observed are a special case, confined to either early
learning, or to avian species. Whilst there are undoubtedly features
which are specific to both, I would argue that our findings are
of more general significance. The striking temporal parallels
between the biochemical cascades found in the hippocampus following
inhibitory avoidance training in rats, and in LTP, with those
described here have been reviewed by Izquierdo and Medina (1997).
The two ‘waves’ of glycoprotein synthesis following
training have been found in a variety of adult mammalian species
and tasks, including appetitive and inhibitory avoidance and motor
learning in mice and rats (Grecksch and Matthies, 1980; Doyle
et al 1992b). The antibodies originally prepared against chick
glycoprotein species, notably NCAM, and which are amnestic when
injected 5.5 hr post-training in our task, are also amnestic when
injected at the same time in rats (Alexinsky, Przybyslawski, Mileusnic,
Rose, and Sara, 1997; Roullet, Mileusnic, Rose, and Sara, 1997;
and see also Doyle, et al. 1992b). However, in these cases amnesia
does not set in until 48hr later, implying some more complex phase
shifts in longer term memory. Indeed one of the clear implications
of the cascade we have found in the chick is that the earlier
heuristic model in which memory formation proceeds serially through
a series of sequential short, intermediate and then finally robust
long-term memory, presumably in the same small ensemble of neurons,
is no longer sustainable, either for the chick or for other species
(DeZazzo and Tully,1995). Furthermore the magnitude and diverse
locations in space and time of the changes we have found following
training on such a simple learning task demands that we reconceptualise
our model of memory storage, moving from a fixed and linear view
of memory formation to a more dynamic concept, involving large
ensembles of cells differentially distributed in space and time
(Rose, 1999).
It
is clear from the diversity of receptor mediated events that can
trigger LTP (eg NMDA and non-NMDA dependence) that we may expect
to find that the processes that initiate synaptic transients are
likely to be task and even species dependent. However, the intracellular
and molecular housekeeping cascades that follow from these transients
may well prove to be more universal, and the final involvement
of CAMs in synaptic remodelling a common feature of many forms
of memory. In elucidating these molecular mechanisms, and in its
potential as a model system for the study of therapeutic approaches
to memory impairment, the chick has earned its proper place amongst
God’s organisms.
|
|
| |
|
|
|
|
|
CONTENTS
The research reviewed here has been supported by the UK Medical
and Biotechonology and Biological Sciences Research Councils,
the Wellcome Trust, the Royal Society and a collaborative programme
funded by the European Science Foundation. I wish to thank my
many colleagues in the Brain and Behaviour Research Group for
the thirty years of collaboration reflected in this review and
the references below.
|
|
|
|
|
|
; |
|
CONTENTS
Alexinsky,
T, Przybyslawski, J, Mileusnic, R, Rose, SPR and Sara, SJ (1997)
Antibody to day-old chick brain glycoprotein produces amnesia
in adult rats Neurobiol. Learn. Mem. 67, 14-20
Ali,
S.M., Bullock, S and Rose, S.P.R. (1988) Phosphorylation of synaptic
proteins in chick forebrain: Changes with development and passive
avoidance training. J. Neurochem. 50, 1579-1587
Andrew,
RJ (ed) (1991) Neural and Behavioural Plasticity: the use of
the Domestic Chick as a Model Oxford University Press
Andrew,
RJ (1999) The differential role s of right and left sides of the
brain in memory formation Behav. Brain Res 88, 289-296
Andrew,
RJ and Rogers, LJ (1972) Testosterone, search behaviour and persistence
Nature, 237, 343-346
Anokhin,
K.V., Mileusnic, R, Shamakhina, I.Y. and Rose, S.P.R. (1991) Effects
of early experience on c-fos gene expression in the chick forebrain.
Brain Res. 544 101-107
Anokhin,
K.V. and Rose, S.P.R. (1991) Learning-induced increase of immediate
early gene messenger RNA in the chick forebrain. Eur. J. Neurosci.
3 162-167
Bailey,
CH and Kandel, ER (1993) Structural changes accompanying memory
storage Ann. Rev. Physiol. 55, 397-426
Barber,
A., Gilbert, D.B. and Rose, S.P.R. (1989) Glycoprotein synthesis
is necessary for memory of sickness-induced learning in chicks.
Eur. J. Neurosci. 1, 673-677
Barber,
TA, Howorth, PD, Klunk,AM and Cho, CC (1999) Lesions of the intermediate
medial hyperstriatum ventrale impair sickness conditioned learning
in day old chicks Neurobiol. Learn. Mem. 72, 128-141
Bateson,
PPG (1966) The Characteristics and Context of Imprinting Biol.
Rev. 41, 177-220
Bliss,
TVP and Collingridge, GL (1993) A synaptic model of memory: Long-term
potentiation in the hippocampus Nature, 361, 31-39
Bradley,
PM, Burns,BD, King, TM and Webb, AC (1999) Electrophysiological
correlates of past history: in vitro studies of the IMHV of domestic
chick Bheav. Brain Res, 98, 261-266
Braun,
K, Bock, J, Metzger, M, Jiang, S and Schnabel, R (1999) The dorsal
neostriatum of the domestic chick: a structure serving higher
associative functions Behav. Brain Res. 98, 211-218
Bullock,
S., de Graan, P.N.E., Oestreicher, A.B., Gispen, W.H. and Rose,
S.P.R. (1990) Identification of a 52kDa chick brain membrane protein
showing changed phosphorylation after passive avoidance training
as B50 (GAP 43). Neurosci. Res. Comm.6, 181-186
Burchuladze,
R, and Rose, SPR (1992) Memory formation in day old chicks requires
NMDA but not non-NMDA glutamate receptors. Eur.J.Neurosci.
4 533-538
Burchuladze,
R, Potter, J and Rose, S.P.R. (1990) Memory formation in the chick
depends on membrane-bound protein kinase C. Brain Res.535,
131-138
Burne,
THJ and Rose, SPR (1997) Effects of training procedure on memory
formation using a weak passive avoidance learning paradigm. Neurobiol.
Learn. Mem. 68, 133-139
Chang,
FLF and Greenough, WT (1984) Transient and enduring morphological
correlates of synaptic activity and efficacy change in rat hippocampal
slices Brain Res. 309, 35-46
Cherkin,
A (1969) Kinetics of memory consolidation; role of amnestic treatment
parameters. Proc Nat Acad Sci US 63, 1094-1101
Clements,
MP and Bourne RC (1996) Passive avoidance learning in the day
old chick is modulated by GABAergic agents Pharmacol. Biochem.
Behav. 53, 629-634
Clements
MP and Rose SPR (1996) Time dependent increase in release of arachidonic
acid following passive avoidance training in the day-old chick
J Neurochem. 67, 1317-1323
Clements,
MP, Rose, SPR and Tiunova, A (1995).wConotoxin GVIA disrupts memory
formation in the day old chick Neurobiol. Learn.Mem. 64
276-284
Csillag,
A (1999) Striato-telencephalic and striato-tegmental circuits:
relevance to learning in domestic chicks Behav. Brain Res.
98, 227-237
Crowe,
SF, Zhao,W-Q, Sedman, GL and Ng, KT (1994) 2-deoxygalactose interferes
with an intermediate processing stage of memory Behav. Neural
Biol. 61, 206-213
Daisley,
JN and Rose, SPR (1994) The effect of a passive avoidance task
on the release of amino acids in vitro from the left IMHV of the
day old chick. Biochem. Trans. 22, 160S
Daisley,
JN, Gruss, M, Rose, SPR and Braun, K (1998) Passive avoidance
training and recall are associated with increased glutamate levels
in the IMHV of the day old chick Neural Plasticity, 6,41-52
Damasio,
AR (1994) Descartes Error: emotion, reason and the human
brain.London, Macmillan
Davies,
HP and Squire,LR (1984) Protein synthesis and memory: a review
Psychol. Bull. 96, 518-559
DeZazzo,
J and Tully, T (1995) Dissection of memory formation. From behavioral
pharmacology to molecular genetics. Trends Neurosci. 18,
212-217
Doyle,
E, Nolan, P, Bell, R and Regan, CM (1992a) Neurodevelopmental
events underlying information acquisition and storage Network,
3, 89-94
Doyle,
E, Nolan, P, Bell, R and Regan, CM (1992b) Intraventricular infusions
of anti-neural cell adhesion molecule in a discrete post-training
period impair consolidation of a passive avoidance response in
the rat J, Neurochem. 59, 1570-1573
Edelman,
GM (1985) Cell adhesion and the molecular process of morphogenesis
Ann. Rev Biochem. 54, 135-169
Freeman,
FM and Rose, SPR (1995) Two time windows of anisomycin-induced
amnesia for passive avoidance training in the day old chick Neurobiol.
Learn. Mem .63, 291-295
Freeman,
W (1999) How Brains Make up their Minds,Weidenfeld and
Nicolson, London
Gibbs,
ME and Ng, KT (1977) Psychobiology of memory: Towards a model
of memory formation. Behav, Rev. 1, 113-136
Gibbs,
ME, Ng, KT and Crowe, S (1991) Hormones and the timing of phases
of memory formation. In Andrew, RJ (ed) Neural and Behavioural
Plasticity: the use of the Domestic Chick as a Model Oxford
University Press, pp440-455
Gilbert,
D.B., Patterson, T.A., and Rose, S.P.R. (1989) Midazolam induces
amnesia in a simple one-trial maze-learning task. Pharmacol.
Biochem. Behav. 34, 439-442
Goelet,
P, Castelluci, S, Schachner, S and Kandel, ER (1986) The long
and the short of long-term memory — a molecular framework
Nature 322, 419-423
Grecksch,
G and Matthies, H-J (1980) Two sensitive periods for the amnestic
effect of anisomycin Pharmacol. Biochem Behav. 12, 663-665
Gruss,
M and Braun, K (1996) Stimulus-evoked increase of glutamate in
the mediorostral neostratum/hyperstriatum ventrale of domestic
chick after auditory imprinting: an in vivo microdialysis study.
J. Neurochem. 66, 1167-1173
Holscher,
C and Rose, SPR (1993) Inhibiting synthesis of the putative retrograde
messenger nitric oxide results in amnesia in a passive avoidance
task in the chick. Brain Res. 619,189-194
Holscher,
C and Rose, SPR (1994) Inhibitors of phospholipase A2 produce
amnesia for a passive avoidance task in the chick. Behav.Neural
Biol. 61, 225-232
Horn,
G (1985) Memory, Imprinting and the Brain , Oxford University
Press
Huber,
G, Martin, JR, Lofler, J and Moreau, J-L (1993) Involvement of
amyloid precursor protein in memory formation in the rat:L an
indirect antibody approach Brain Res. 603, 348-352
Izquierdo,
I. & Medina, J.H.(1997) Memory formation: the sequence of
biochemical events in the hippocampus and its connection to activity
in other brain structuresNeurobiol. Learn. Memory 68,
285-316
Johnston
ANB, Burne, THJ and Rose, SPR (1999) Observation learning in day-0old
chicks using a one-trial passive avoidance learning paradigm.
Anim. Behav. 56, 1347-1353
Johnston,
ANB and Rogers, LJ (1998) Right hemisphere involvement in imprinting
memory revealed by glutamate treatment. Pharmacol. Biochem.
Behav. 60, 863-871
Johnston,
ANB and Rose, SPR (1998) Isolation-stress induced facilitation
of passive avoidance memory in the day-old chick Behav. Neurosci.
112, 1-8
Johnston,
ANB, Clements, MP and Rose, SPR (1999) Role of brain-derived neurotrophic
factor and presynaptic proteins in passive avoidance learning
in day old domestic chicks. Neurosci. 66, 1033-1042
Konishi,M
(1989) Bird song for neurobiologists Neuron, 3, 541-549
Kossut,
M and Rose, SPR (1984) Differential 2-deoxyglucose uptake into
chick brain structures during passive avoidance training Neurosci.
12, 971-977
Krebs,
JR, Sherry, DF, Healy, SD, Perry, VH and Vaccarino, AL (1989)
Hippocampal specialisation of food storing birds Proc. Natt.
Acad. Sci. US, 86, 1388-1392
Lancashire,
C, Mileusnic, R and Rose, SPR (1998) Apolipoprotein antibodies
affect the retention of passive avoidance memory. Neural Plasticity,
6, 29-40
Lorenz,
K (1935) Der Kumpan in der Umwelt des Vogels J.Ornithol..
83, 137-213; 289-413
Loscertales,
M. Rose, SPR and Sandi, C (1997) The corticosteroid synthesis
inhibitors metyrapone and aminoglutethimide block long-term memory
for a passive avoidance task in day-old chicks Brain Res.,
769, 357-361
Lossner,
B. and Rose, S.P.R.(1983) Passive avoidance training increases
fucokinase activity in right forebrain base of day-old chicks.
J. Neurochem. 41 , 1357-1363.
Luthi,
A, Laurent, JP, Figurov, A, Muller,D and Schachner, M (1994) Hippocampal
long term potentiation and neural cell adhesion molecules L1 and
NCAM Nature, 372, 777-779
McCabe,
BJ and Nicol, AU (1999) The recognition memory of imprinting:
biochemistry and electrophysiology,Behav. Brain Res.98,
253-260
McKay,
SE, Purcell, AL and Carew, TJ (1999) Regulation of synaptic function
by neurotrophic factors in vertebrates and invertebrates: implications
for development and learning. Learn. Mem. 6, 193-215
McGaugh,
JL (1989) Involvement of hormonal and neuromodulatory systems
in the regulation of memory storage. Ann. Rev. Neurosci. 12,
255-287
Marler,
P (1991) Song learning behavior: the interface with neuroethology
Trends Neurosci. 14, 199-206
Matthies,
H-J (1989) In search of the cellular mechanisms of memory Prog.
Neurobiol.32, 277-349
Mileusnic,
R, Anokhin, K and Rose, SPR (1996) Antisense oligodeoxynucleotides
to c-fos are amnestic for passive avoidance in the chick NeuroReport,
7, 1269-1272
Mileusnic,
R, Lancashire, C and Rose, SPR (1999) Sequence specific impairment
of memory formation by NCAM antisense oligonucleotides Learning
and Memory 6,120-127
Mileusnic,
R, Lancshire, C, Johnston, ANB and Rose, SPR (1999) Antibodies
and antisense to the amyloid precursor protein (b-APP) prevent
memory consolidation:RERMS peptide rescues in preparation
Mileusnic,
R, Rose, SPR, Lancashire, C and Bullock, S (1995) Characterisation
of antibodies specific for chick brain NCAM which cause amnesia
for a passive avoidance task J. Neurochem.64 2598-2605
Ng,
KT and Gibbs, ME (1991) Stages in memory formation: a review.
In Andrew, RJ (ed) Neural and Behavioural Plasticity: the use
of the Domestic Chick as a Model Oxford University Press,
pp351-369
Nottebohm,
F (1970) Ontogeny of bird song Science, 167, 950-956
Nottebohm,
F (1980) Brain pathways for vocal learning in birds: A review
of the first ten years Progress in Psychobiology and Physiological
Psychology, 9, 85-124
Patel,
S.N., Rose, S.P.R., and Stewart, M.G. (1988) Training induced
dendritic spine density changes are specifically related to memory
formation processes in the chick, gallus domesticus. Brain
Research 463, 168-173
Patterson,
TA, Alvarado, MC, Rosenzweig, MR and Bennett, EL (1988) Time courses
of amnesia development in two different areas of the chick brain
Neurochem. Res. 10, 1071-1081
Patterson,
TA and Rose, SPR (1992) Memory in the chick: multiple cues, distinct
brain locations. Behavioural Neuroscience, 106, 465-470
Pollerberg,
GE, Sadoul, R, Goridis, C and Schachner, M (1985) Selective expression
of the 180-kD component of the neural cell adhesion molecule NCAM
during development J. Cell Biol. 101. 1921-1929
Popov,
NS, Schulzeck, S, Pohle, W and Matthies, H-J (1981) Changes in
the incorporation of 3H-fucose into rat hippocampus after acquisition
of a brightness discrimination reaction: an electrophoretic study
Neuorscience, 5, 161-165
Purves,
D (1988) Body and Brain: a trophic theory of neural connections
Harvard University Press, Cambridge Ma
Regolin,
L and Rose, SPR (1999) Long-term memory for a spatial task in
young chicks Anim. Behav. 57, 1185-1191
Rickard,
NS, Poot, AC, Gibbs, ME and Ng, KT (1994) Antagonism of iether
NMDA or non-NMDA glutamate receptors impairs long-term memory
consolidation in the day-old chick Behav. Neural Biol.
62, 33-40
Rickard,
NS.; Ng, KT. & Gibbs, ME. (1998). Further support for nitric
oxide-dependent memory processing in the day-old chick. Neurobiol.
Learn. Memory. 69; 79-86.
Rogers,
LJ (1995) The Development of Brain and Behaviour in the Chicken
CAB International, Wallingford, UK
Rogers,
LJ and Deng, C (1999) Light experience and the lateralisation
of two visual pathways in the chick. Behav. Brain Res.
88 277-288
Rose,
SPR (1995a) Glycoproteins and memory formation Behav. Brain
Res. 66 73-78
Rose,
SPR (1995b) Cell adhesion molecules, glucocorticoids and memory
Trends Neurosci. 18, 502-506
Rose,
SPR (1999) Time dependent processes in memory revisited Behav.
Neurosci. In press
Rose,
S.P.R. and Harding, S.(1984) Training increases 3H Fucose incorporation
in chick brain only if followed by memory storage. Neurosci
12, 663-667.
Rose,
S.P.R. and Jork, R.(1987) Long-term memory formation in chick
is blocked by 2-deoxygalactose, a fucose analogue. Behav.Neural.Biol.
48, 246-258
Rose,
SPR and Stewart, MG (1999) Cellular correlates of memory formation
in the chick following passive avoidance training Behav. Brain
Res. 98, 237-243
Roullet.
P. Mileusnic, R, Rose, SPR and Sara, SJ (1997) Neural cell adhesion
molecules play a role in rat memory formation in appetitive as
well as aversive tasks Neuroreport, 8, 1907-1911
Rusakov,
DA, Davies, HA, Krivko, IM, Stewart MG and Schachner, M (1994)
Training alters patterns of PSA-NCAM in chick forebrain membranes
NeuroReport 5, 2467-2473
Salinska,
EJ, Bourne,RC and Rose, SPR (2000) Long-term memory formation
in the chick requires mobilisation of ryanodine sensitive intracellular
calcium stores. Neurobiology of Learning In Press
Salinska,
EJ, Chaudhury, D, Bourne, RC and Rose, SPR (1999) Passive avoidance
training results in increased responsiveness of synaptosomal voltage
and ligand gated channels in chick brain Neuroscience In
press
Sandi,
C, and Rose, S.P.R. (1994a) Corticosterone enhances long-term
retention in one day old chicks trained in a weak passive avoidance
learning paradigm. Brain Res.647, 106-112
Sandi,
C and Rose, SPR (1994b) Corticosteroid receptor antagonists are
amnestic for passive avoidance learning in day-old chicks Eur.
J. Neurosci. 6, 1292-1297
Sandi,
C and Rose, SPR (1997a) Training-dependent biphasic effects of
corticosterone in memory formation for a passive avoidance tasks
in chicks. Psychopharmacology 133, 152-160
Sandi,
S and Rose, SPR (1997b) Protein synthesis and fucosylation-dependent
mechanisms in corticosterone facilitation of long-term memory
in the chick Behav. Neurosci.111, 1-7
Sandi,
C, Rose, SPR, Mileusnic, R and Lancashire, C (1995) Corticosterone
facilitates long-term memory formation via enhanced glycoprotein
synthesis Neuroscience, 69, 1087-1093
Scheich,
H (1987) Neural correlates of auditory filial imprinting J.
Comp. Physiol. 161, 605-9
Scholey,
AB, Mileusnic, R, Schachner, M and Rose, SPR (1995) A role for
a chicken homolog of the neural cell adhesion molecule L1 in consolidation
of memory for a passive avoidance task Learn. Mem. 2,17-25
Scholey,
AB, Rose, SPR, Zamani, MR, Bock, E and Schachner, M (1993) A role
for the neural cell adhesion molecule in a late consolidating
phase of glycoprotein synthesis 6hr following passive avoidance
training of the young chick Neuroscience 55, 499-509
Serrano,
PE,Beniston, DS, Oxonian, MG, Rodriguez, WA, Rosenzweig,MR and
Eennett, EL (1994) Differential effects of protein kinase inhibitors
and activators on memory formation in the 2-day old chick Behav.
Neural Biol. 61, 60-72
Singer,
W (2000) In Changing Concepts of Nature at the Millennium,
Cambridge University Press, forthcoming
Skibo,
GG, Davies, HA, Rusakov, DA, Stewart, MG and Schachner, M (1993)
Increased immunogold labelling of NCAM isoforms in synaptic active
zones of the chick striatum 5-6hr after one-trial passive avoidance
training Neuroscience, 82, 1-5
Solomonia,
RO, McCabe, BJ and Horn, G (1995) A time-dependent, larning specific
increase in the amount of neural cel adheison molecules (NCAMs)
in chick forebrain after visual imprinting J.Physiol.,
485, P8
Steele,
RJ and Stewart, MG (1995) Involvement of AMPA receptors in maintenance
of memory for a passive avoidance task in day-old domestic chicks
(Gallus domesticus) Eur. J. Neurosci.,7, 1297-1304
Steele,
RJ, Stewart, MG and Rose, SPR (1995) Increases in NMDA receptor
binding are specifically related to memory formation for a passive
avoidance task in the chick: a quantitative autoradiographic study.
Brain Res. 674, 352-356
Stewart
, MG, Bourne, RC and Steele, RJ (1992) Quantitative autoradiographic
demonstration of changes in binding to NMDA sensitive 3H glutamate
and 3H MK801 but not 3H AMPA receptors in the chick forebrain
30 minutes after passive avoidance training Eur. J. Neurosci.
4, 936-943
Stewart,
MG and Rusakov, DA (1995) Morphological changes associated wirth
stages of memory formation in the chick following passive avoidance
training Behav. Brain Res. 12, 21-28
Tiunova,
A, Anokhin, KV and Rose, SPR (1998) Two critical periods of protein
and glycoprotein synthesis in memory consolidation for visual
categorisation learning in chicks. Learn. Mem. 4, 401-410
Wallhauser,
E and Scheich, H (1987) Auditory imprinting leads to differential
2-deoxyglucose uptake and dendritic spine loss in the chick rostral
forebrain Devel. Brain Res. 31, 29-44
|
|
|
CONTENTS
|
|
|
|
|
|
|
