TY - JOUR TI - Associative properties of the perirhinal network DO - https://doi.org/doi:10.7282/T3CC0ZMZ PY - 2012 AB - The perirhinal cortex (PRC), comprised of Brodmann areas 35 and 36, is a rostrocaudally-oriented strip of cortex in the medial temporal lobe, whose lesion produces memory impairments. Previous in vivo recording studies have revealed that a reduction in the responsiveness of perirhinal neurons to familiar stimuli underlies object recognition memory; whereas the opposite behavior, an increase in responsiveness, is required for associative memory formation between two paired stimuli. Both phenomena rely on long-term plasticity in the PRC. However, it is currently unclear how, as a result of experience, the same network could support these two seemingly opposite forms of long-term plasticity. PRC receives topographically organized projections from many high-order neocortical areas, mostly from the adjacent temporal neocortex; and it possesses an intrinsic network that distributes these neocortical inputs throughout its rostrocaudal axis. Previous studies suggest that neocortical inputs strongly recruit perirhinal inhibitory interneurons located at the same transverse level. In contrast, distant neocortical inputs only lead to excitation because longitudinal perirhinal connections engage few inhibitory interneurons. Given these facts, it is possible that the PRC acts as a Hebbian network to associate coincident but spatially distributed inputs. Consequently, the main objective of this thesis is to shed light on the mechanisms allowing neocortical inputs to undergo long-term depression (LTD) or potentiation (LTP), depending on to what extent they recruit the intrinsic perirhinal connections. Thus, using electrophysiological and imaging techniques in the whole guinea pig brain in vitro, I show that theta-frequency stimulation (TFS) at a single neocortical site leads to an input-specific group I mGluR-dependent LTD at all perirhinal levels, whereas paired TFS of two distant neocortical sites recruits the intrinsic circuit of the PRC and results in a NMDAR-dependent LTP to the paired inputs. Consistent with these results, utilizing anterograde tracing in rats and electron microscopic observations, this thesis shows that there are more inhibitory synapses formed by direct neocortical inputs to PRC and short-range perirhinal connections compared to long-range neocortical and perirhinal axons coursing in the PRC. Together, these findings suggest a mechanism whereby PRC associates temporally relevant but spatially distributed neocortical inputs. KW - Neuroscience KW - Temporal lobes KW - Cerebral cortex--Anatomy KW - Memory disorders LA - eng ER -