Book of abstracts - British Neuroscience Association

56.02
The acquisition and consolidation of recognition memory are
neurotrophin-dependent
Callaghan C K, Kelly A M
Department of Physiology and Trinity College Institute of
Neuroscience, Trinity College, Dublin 2, Ireland.
Acquisition and consolidation of newly-acquired information is
essential for formation of long-lasting memories, and both these
processes may share common signaling pathways. The neurotrophins
NGF, BDNF, NT3 and NT4 have diverse functions in the adult brain,
including learning and memory. Their biological effects are elicited by
binding to Trk receptors. In this study we investigated the roles of
neurotrophins in both acquisition and consolidation of memory by
using neutralising antibodies against each neurotrophin isoform.
An object recognition task was used to test acquisition and
consolidation of memory; rats were tested 10min and 24hr after
training to discriminate experimentally between acquisition and
consolidation respectively. Male Wistar rats (n=12) were implanted
with cannulae for administration of pharmacological agents to the third
ventricle. Rats were injected with antiNGF, antiBDNF, antiNT3,
antiNT4 or control serum (5ƒÝl), or the pan-Trk inhibitor
TyrphostinAG879 or vehicle control, one hour before training in the
task.
Rats treated with TyrphostinAG879 were unable to discriminate
between the novel and the familiar object at both 10min and 24hr
when compared with controls, suggesting Trk receptor activation is
required for both acquisition and consolidation. In contrast, rats treated
with anti-BDNF, anti-NGF and anti-NT 4 displayed comparable
learning to control rats at the 10min timepoint, but displayed learning
impairments 24hr later. Treatment with anti-NT3 had no effect on
learning at either timepoint.
Neurotrophins appear to play an important role in both acquisition and
consolidation of recognition memory. Further experiments are required
to assess the precise signaling mechanisms involved in such plastic
events.
56.03
The role of NMDA receptors in learning and memory
Belsham A A G, Darlison M G, Freeman F M
School of Biomedical and Natural Sciences, Nottingham Trent University,
Clifton Campus,, Nottingham, NG11 8NS ,
The N-methyl-D-aspartate receptor (NMDAR) is involved in the early stages
of long-term memory formation (LTMF). NMDAR stimulation causes Ca2+
influx, resulting in plasticity. NMDARs in the chick (Gallus domesticus)
forebrain predominantly comprise of NR1 and either NR2A or NR2B
subunits. NR2B containing receptors demonstrate higher Ca2+
conductance compared to those containing NR2A. Increased neuronal
activity causes NR2A receptor subtypes to be internalised and replaced
with those containing NR2B. The current study investigates this activitydependent
switch on a molecular level using radioactive in situ
hybridisation to quantify levels of mRNA encoding the NR1, NR2A and
NR2B genes in the chick forebrain at significant time points during LTMF.
Both the intermediate medial mesopallium (IMM), a sensory information
sorting centre, and the medial striatum (MSt), which is involved in the
suppression of pecking behaviour, show changes in mRNA levels encoding
the NMDAR subunits at time points when they become activated during
LTMF. These changes may reflect the activity dependent switch between
NR2A and NR2B subtypes. In addition, this exchange of receptor subtypes
is investigated using behavioural pharmacology. Ligands specific for NR2A
and NR2B receptor subtypes were injected into specific regions of the
forebrain at relevant time points pre- and post-training. The effects of these
subtype specific ligands on task recall and discrimination are presented
here.
56.04
Motor dysfunction, and impairments in short-term memory and
synaptic plasticity in a mouse model (Tc1) of Down syndrome
Morice E. (1), Cooke S.F. (1), Vanes L. (2), Fisher E. M. C. (3),
Tybulewicz V. (2), Bliss T. V. P. (1)
(1) Division of Neurophysiology, NIMR, The Ridgeway, Mill Hill,
London NW7 1AA UK; (2) Division of Immune Cell Biology, NIMR, The
Ridgeway, Mill Hill, London NW7 1AA UK; (3) Department of
Neurodegenerative Disease, Institute of Neurology, Queen Square,
London WC1N 3BG UK
Down syndrome (DS) is a genetic disorder arising from the presence
of a third copy of human chromosome 21 (Hsa21). Recently,
O’Doherty et al (2005) generated a trans-species aneuploid mouse
line (Tc1) that carries an almost complete Hsa21 chromosome. The
Tc1 mouse is the most complete animal model for DS currently
available. Tc1 mice show many features that relate to human DS,
including alterations in learning, synaptic plasticity, cerebellar neuronal
number, heart development, and mandible size. Because motor
deficits and mental retardation are among the most frequently
occurring features of DS, we have undertaken a more detailed
analysis of motor and cognitive functions, and hippocampal long-term
potentiation (LTP) of Tc1 mice. Our results reveal that, compared to
controls, Tc1 mice exhibit a higher novelty-driven spontaneous activity
and a major deficit in motor coordination in a cerebellum-dependent
learning task. In the Morris water maze, Tc1 mice display intact spatial
long-term memory in a probe trial 20 days after the last training
session. However, Tc1 mice are severely impaired in a working
memory version of the task. In addition, we demonstrate reduced LTP
but normal maintenance over days in the dentate gyrus of freely
moving Tc1 mice. Thus, the deficits in synaptic plasticity are paralleled
by corresponding deficits in memory: short-term plasticity and shortterm
memory are impaired, whereas long-term plasticity and long-term
memory are unaffected.
56.05
Post-training intrahippocampal infusion of nicotine-bucladesine
combination causes a synergistic enhancement effect on spatial
memory retention in rat
Gholizadeh S, Sharifzadeh M, Zamanian A R, Zarrindast M R, Roghani A
1.Dept. of Toxicology and Pharmacology, School of Pharmacy,
Pharmaceutical Sciences and Medicinal plants research Centers, Tehran
University of Medical Sciences, Tehran, Iran, 2.Department of
Pharmacology and Neuroscience, Texas Tech University Health Sciences
Center,Lubbock, TX, USA
We previously had shown that bilateral intrahippocampal infusion of 1 µg
nicotine (but not 0.5 µg dose) led to an improvement in spatial memory
retention in the Morris water maze task in male rats. We also reported that
a similar type of bilateral infusion of H89, a protein kinase AII (PKA II)
inhibitor, caused a deficit in spatial memory retention. In the present study,
we wished to test the hypothesis that intrahippocampal infusion of dibutyryl
cyclic AMP (DB-cAMP also called bucladesine), a membrane permeable
selective activator of PKA, into the CA1 region can cause an improvement
in spatial memory in this maze task. Indeed, bilateral infusion of 10 and 100
µM bucladesine (but not 1 and 5 µM doses) led to a significant reduction in
escape latency and travel distance (showing an improvement in spatial
memory) compared to the control. Also, bilateral infusion of 0.5 µg nicotine
or 1 µM bucladesine alone did not lead to an improvement in spatial
memory. However, such bilateral infusion of bucladesine at 1 and 5 µM
concentrations infused within minutes after 0.5 µg nicotine infusion
improved spatial memory retention. Taken together, our data suggest that
intrahippocampal bucladesine infusions improve spatial memory retention
in male rats and that bucladesine can interact synergistically with nicotine
to improve spatial memory.
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