Impaired fear memory, altered object memory and modified hippocampal synaptic plasticity in split-
By: Peter MacPherson, Ruth McGaffigan, Douglas Wahlsten, Peter V. Nguyen
MacPherson, P., McGaffigan, R., Wahlsten, D., and Nguyen, P.V. (2008) Impaired fear memory, altered object
memory and modified hippocampal synaptic plasticity in split-brain mice. Brain Research, 1210: 179-188.
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The hippocampus is critical for memory formation. However, the contributions of the hippocampal commissure
(HC) and the corpus callosum (CC) are less clear. To elucidate the role of the forebrain commissures in learning
and memory, we performed a behavioural and electrophysiological characterization of an inbred mouse strain
that displays agenesis of the CC and congenitally reduced HC (BTBR T+ tf/J; „BTBR‟). Compared to a control
strain, BTBR mice have severely impaired contextual fear memory, with normal object recognition memory.
Interestingly, continuous environmental “enrichment” significantly increased object recognition in BTBR, but
not in control C57BL/6 („BL/6‟) mice. In area CA1 of hippocampal slices, BTBR displayed intact expression of
long-term potentiation (LTP), paired-pulse facilitation (PPF) and basal synaptic transmission, compared to BL/6
mice. However, BTBR hippocampal slices show an increased susceptibility to depotentiation (DPT), an
activity-induced reversal of LTP. We conclude that the HC and CC are critical for some forms of hippocampal
memory and for synaptic resistance to DPT. Agenesis of the CC and HC may unmask some latent ability to
encode, store or retrieve certain forms of recognition memory. We suggest that the increased susceptibility to
DPT in BTBR may underlie the memory phenotype reported here.
Keywords: Hippocampal commissure, Corpus callosum, Memory, Synaptic plasticity, LTP, Mouse strain
Systematic surveys of multiple inbred strains have identified extreme phenotypes that can enhance our
understanding of brain function. Unique among all mouse strains studied to date (Wahlsten et al., 2003b), the
BTBR T+ tf/J („BTBR‟) strain always lacks a corpus callosum (CC) and has severely reduced hippocampal
commissure (HC). Two X chromosome regions contribute to the anatomical defect of the BTBR forebrain
(Kusek et al., 2006). Although there is a significant but small increase in the number of unmyelinated axons in
the anterior commis-sure when the CC is absent (Livy et al., 1997), this compensatory increase is dwarfed by
the massive loss of connectivity between the hemispheres in BTBR mice.
Here we report the first electrophysiological study of the hippocampus in these animals and find that most
measures are remarkably normal. On two very different tests of mouse memory, BTBR mice show substantial
deficits in contextual fear conditioning but not object recognition memory. These findings indicate that the
commissural system is not important for most aspects of normal ipsilateral function of the hippocampus but
may nonetheless be involved in the formation of certain kinds of long-term memories in these mice.
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