Book of abstracts - British Neuroscience Association

37.05
Hippocampal maps are true neural objects: Evidence from
combined place cell recordings and the cellular distribution of
immediate early gene Mrna
Roberts* L, Habibian-Dehkordi S, Masih N, Rivard B, Muller R
MRC Centre for Synaptic Plasticity, Department of Anatomy,
University of Bristol, BS8 1TD., *current address: St Georges,
University of London, Cranmer Terrace, London, SW17 0RE
From electrophysiological evidence, the rat hippocampus is believed
to form a map-like representation of each different environment. Each
map is a randomly selected subset of hippocampal pyramidal cells
called “place cells” each discharging only within a cell- and
environment-specific region - its “firing field”. Each subset is a unit
since its cells fire together in only one environment but perhaps the
cells in a map are also linked to each other more directly. To test this
possibility we recorded place cells twice from individual rats, in a
cylinder and later in half the cylinder; recordings were made in the
reverse order in other rats. In all cases cells had the same fields in the
half as in the whole cylinder; the map was preserved. We then used
“cellular analysis of temporal activity by fluorescent in situ
hybridisation” (catFISH) to visualize mRNA from the immediate early
gene ARC. Cytoplasmic fluorescence indicates that ARC was
activated during the earlier exposure; nuclear fluorescence indicates
activation during the later exposure. The key finding is that the same
number of cells was labelled at the early and late time points,
regardless of the order of exposure. Thus, even though only half the
place cells discharge in the half cylinder, by another measure the
entire subset is activated! We conclude that the map has its own
structural identity – it is a neural entity and not merely a collection of
independent place cells. All procedures were performed in accordance
with the Animals (Scientific Procedures) Act 1986.
37.06
Depth profiles of antidromic and orthodromic responses evoked in
hippocampal subfield CA1 by entorhinal stimulation
Vorobyov N A, Brown M W
MRC Centre for Synaptic Plasticity, Department of Anatomy, University of
Bristol, Bristol, BS8 1TD, UK
Transmission of activity between the entorhinal cortex and hippocampus is
central to operation of the hippocampal memory system. Previously we
reported that electrical stimulation of entorhinal cortex evoked spatially
separated antidromic and orthodromic responses in the pyramidal layer of
CA1, indicating that entorhinal cortex could successively transfer activity
from one part of CA1 to another (Vorobyov and Brown, FENS 2004, p.402).
Here we establish that the differences between antidromic and orthodromic
responses do not arise from the reversal of potentials within CA1 or from
volume conduction from the underlying dentate gyrus.
We recorded simultaneously using multiple electrodes responses from
layers at different depths within CA1 and from the underlying molecular
layer of dentate gyrus in rats. The findings established that there was no
reversal of the potentials for either antidromic or orthodromic responses
throughout the depth of CA1. Both the negative potential of orthodromic
responses and the positive potential of antidromic responses were larger in
deeper compared to superficial layers. Increasing the stimulation intensity
resulted in an increase in the amplitude of responses but did not change
their shape and depth profile. Responses evoked in CA1 differed in shape
from those in the underlying dentate gyrus and changed size independently
of them.
Thus neither antidromic or orthodromic responses reversed through the
depth of CA1 and these CA1 responses were independent of potentials in
the underlying dentate gyrus. Accordingly, the previously described
differences between antidromic and orthodromic responses reflect
differences in the origin of these responses.
Supported by The Wellcome Trust.
37.07
The effect of 5-Fluorouracil and environmental enrichment on
recognition memory and cell proliferation in the adult rat
hippocampus.
Mustafa S, Wigmore P, Bennett G
Institute of Neuroscience, School of Biomedical Sciences, University
of Nottingham, Queen’s Medical Centre, , Nottingham, NG7 2UH
‘Chemobrain’ describes the cognitive deficits in adults which are
prevalent with systemic chemotherapy using agents such as 5-
Fluorouracil (5-Fu) that disrupts cell proliferation by interfering with
DNA synthesis. Proliferating cells are found within the adult dentate
gyrus (DG) of the hippocampus and give rise to new neurons that are
involved in memory and learning. A significant proportion of these
proliferating cells are associated with vascular endothelial cells. We
hypothesise that 5-Fu may affect proliferating cells in the adult DG and
cause deficits in hippocampal-mediated memory and this may be
modulated by environmental enrichment.
In this study, ‘chemobrain’ is modelled in rats by chronic systemic 5-Fu
administration. The effects of 5-Fu treatment and environmental
enrichment on hippocampal recognition and location memory were
observed using novel object and object location recognition memory
tasks, respectively. Immunohistochemistry with Ki67 and RECA-1
antibodies was used to measure the numbers of vascular-associated
(VA) and non-vascular associated (NVA) proliferating cells.
5-Fu treatment disrupted long-term recognition memory as indicated
by decreased novel object recognition, which was enhanced by
environmental enrichment, and also affected location recognition
memory. On-going measurement of proliferating cells in the DG is
being correlated with these behavioural changes to determine if 5-Fu
treatment caused decreases in VA and NVA proliferating cells.
37.08
Phase Precession as a Temporal Code for Trajectory
Huxter J, Allen K, Senior T, O`Neill J, Csicsvari J
MRC Anatomical Neuropharmacology Unit, Mansfield Road, Oxford, OX1
3TH, United Kingdom,
Pyramidal cells ("place cells") in the dorsal hippocampus have spatially
selective firing fields. In addition, as a rat traverses a given cell’s place field,
the cell fires at progressively earlier phases of each successive theta cycle.
This “phase precession” improves location prediction on tasks where rats
are trained to run in stereotyped trajectories. It has also been proposed as
a mechanism by which sequences of locations along a trajectory may be
learned, and a means of facilitating LTP. However, phase precession has
been poorly characterised in tasks where animals can move more freely,
and it is not clear what type of information this temporal code may carry
during non-stereotyped running. To address these questions, we
characterized phase precession in a large number of pyramidal cells in a
random foraging task. We identified robust monotonic phase precession,
regardless of the direction in which place fields were crossed. In agreement
with previous findings, the distance travelled through the place field was the
best predictor of firing phase. Moreover, using a Bayesian maximum
likelihood method, we were able to reconstruct movement trajectory from
the firing phases of a population of place cells. This represents the first
direct evidence of a hippocampal signal for the direction in which the animal
is moving. Taken together with the existence of place cells and the
modulation of their firing rates by running speed, this has important
implications for models of the hippocampus as a path integrator, and
demonstrates the utility of simultaneous rate and temporal coding.
Further studies are required to confirm if 5-Fu-induced changes in DG
proliferating cells are associated with disruption of hippocampusmediated
memory. This animal model of ‘chemobrain’ will help
achieve a better understanding of the mechanisms that cause
chemotherapy-associated decline in memory.
Page 56/101 - 10/05/2013 - 11:11:03