Molecular
and Circuit Mechanisms for Hippocampal Memory
We
study molecular, cellular, and
neuronal circuit mechanisms underlying acquisition, consolidation and
retrieval
of hippocampus-dependent memory in rodents. Our primary approach
is to generate cell type and
adult-restricted
knockout mice and characterize them using multifaceted methods
including
molecular and cellular biology, in vitro and in vivo electrophysiology,
confocal
and two photon microscopy and behavioral tasks. The data obtained to
date indicate that NMDA
receptor-mediated synaptic
plasticity in area CA1 plays a pivotal role in special and other
hippocampus
dependent learning and memory. The same
receptors and synaptic plasticity in area CA3 are dispensable for the
acquisition of reference memory, but play an important role in “pattern
completion” – the ability to recall an entire experience with limited
recall cues,
as well as in one trial-based rapid learning. NMDA receptor function in
dentate gyrus (DG) is also
dispensable for
reference memory, but is important in “pattern separation”, the ability
to form
distinct memories of similar events. These
studies attest the power of this
multi-faceted – genetic, physiological and behavioral – approach in
understanding
mechanisms underlying cognition. |
