The perirhinal (PR) cortex is a rostrocaudally-oriented strip of cortex involved in recognition and associative memory. Previous single-unit studies have revealed that PR contributions to recognition memory involve a reduction in the responsiveness of PR neurons to familiar stimuli. In contrast, associative memory formation is dependent on increasing responses of PR neurons to paired stimuli. Both phenomena are thought to reflect activity-dependent changes in synaptic weights within the PR cortex. However, it is currently unclear how the same network could support these two seemingly opposite forms of plasticity. We believe the solution to this paradox resides in the differential connections formed by extrinsic neocortical inputs vs. intrinsic long-range PR connections with feedforward inhibitory interneurons of the PR cortex. Indeed, it was previously shown that neocortical inputs trigger strong feedforward inhibition in PR neurons whereas longitudinal intrinsic pathways mediate apparently pure excitatory responses. Since neocortical inputs can undergo LTD or LTP depending on whether recipient PR cells are hyper- or depolarized, we hypothesize that the polarity (LTD or LTP) of activity-dependent synaptic plasticity in the PR cortex depends on whether PR cells receiving neocortical inputs also receive convergent inputs from the intrinsic system of longitudinal PR connections. This hypothesis will be tested in the following specific aims.
In Aim #1, we will compare the proportion of synapses formed by neocortical axons vs. longitudinal PR axons with GABAergic interneurons using anterograde tracing combined with silver intensified pre-embedding GABA immunocytochemistry.
In Aim #2, we will test whether neocortical stimulation patterns that recruit longitudinal PR connections to different extents lead to activity-dependent LTP or LTD. To test this, in the whole brain kept in vitro by arterial perfusion, we will compare the effects of theta burst stimulation applied at one vs. two distant neocortical sites. Evoked responses will be monitored using extracellular recordings and optical imaging with a voltage sensitive dye.
In Aim #3, we will determine the induction and expression mechanisms of the LTD and LTP induced by focused vs. distributed activation of neocortical inputs using a combination of intracellular recordings and pharmacological manipulations with field potential recordings and optical imaging. The proposed studies will shed light on the inhibitory mechanisms regulating impulse traffic in the rhinal cortices and thus give us unique insights in the factors controlling the propagation of epileptiform activity. Moreover, the proposed work will analyze the network properties that allow the perirhinal cortex to participate in memory formation. Since the rhinal cortices are primarily and/or selectively damaged during early stages of neurological and psychiatric diseases, the basic research program proposed here may improve our understanding of memory disorders.

Public Health Relevance

The proposed studies will shed light on the inhibitory mechanisms regulating impulse traffic in the rhinal cortices and thus give us unique insights in the factors controlling the propagation of epileptiform activity. Moreover, the proposed work will analyze the network properties that allow the perirhinal cortex to participate in memory formation. Since the rhinal cortices are primarily and/or selectively damaged during early stages of neurological and psychiatric diseases, the basic research program proposed here may improve our understanding of memory disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH073610-09
Application #
8415896
Study Section
Special Emphasis Panel (ZRG1-IFCN-L (02))
Program Officer
Osborn, Bettina D
Project Start
2005-06-01
Project End
2015-01-31
Budget Start
2013-02-01
Budget End
2015-01-31
Support Year
9
Fiscal Year
2013
Total Cost
$368,280
Indirect Cost
$130,680
Name
Rutgers University
Department
None
Type
Organized Research Units
DUNS #
130029205
City
Newark
State
NJ
Country
United States
Zip Code
07102
Unal, Gunes; Pare, Jean-Francois; Smith, Yoland et al. (2014) Cortical inputs innervate calbindin-immunoreactive interneurons of the rat basolateral amygdaloid complex. J Comp Neurol 522:1915-28
Unal, Gunes; Pare, Jean-Francois; Smith, Yoland et al. (2013) Differential connectivity of short- vs. long-range extrinsic and intrinsic cortical inputs to perirhinal neurons. J Comp Neurol 521:2538-50
Paz, Rony; Pare, Denis (2013) Physiological basis for emotional modulation of memory circuits by the amygdala. Curr Opin Neurobiol 23:381-6
Popescu, Andrei T; Pare, Denis (2011) Synaptic interactions underlying synchronized inhibition in the basal amygdala: evidence for existence of two types of projection cells. J Neurophysiol 105:687-96
Popa, Daniela; Duvarci, Sevil; Popescu, Andrei T et al. (2010) Coherent amygdalocortical theta promotes fear memory consolidation during paradoxical sleep. Proc Natl Acad Sci U S A 107:6516-9
Popescu, Andrei T; Saghyan, Aleksandr A; Nagy, Frank Z et al. (2010) Facilitation of corticostriatal plasticity by the amygdala requires Ca2+-induced Ca2+ release in the ventral striatum. J Neurophysiol 104:1673-80
Pape, Hans-Christian; Pare, Denis (2010) Plastic synaptic networks of the amygdala for the acquisition, expression, and extinction of conditioned fear. Physiol Rev 90:419-63
Paz, Rony; Bauer, Elizabeth P; Pare, Denis (2009) Measuring correlations and interactions among four simultaneously recorded brain regions during learning. J Neurophysiol 101:2507-15
Popescu, Andrei T; Popa, Daniela; Pare, Denis (2009) Coherent gamma oscillations couple the amygdala and striatum during learning. Nat Neurosci 12:801-7
Popa, Daniela; Popescu, Andrei T; Pare, Denis (2009) Contrasting activity profile of two distributed cortical networks as a function of attentional demands. J Neurosci 29:1191-201

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