The amygdala (AMYG), a key component of the limbic system, is thought to be involved in emotion processing, motivation and learning. These functions result from complex interactions with many other limbic regions such as the anterior cingulate gyrus (ACG), the limbic thalamus (L-THAL) and the hippocampus. Disruption of information processing along these circuits is thought to result in a number of major psychiatric diseases such as schizophrenia, manic depressive and post traumatic stress disorder. The investigations described in this proposal will provide information on the relationships between specific AMYG neuronal subpopulations, their inputs from ACG and the dopaminergic system and their output to the L-THAL. Investigations in rodents (Specific Aims 1-3) are focused on the specific pattern of connections that characterizes neurochemically distinct AMYG neurons. Studies on normal human AMYG (Specific Aim 4) are aimed at creating a bridge between findings in rodents and human postmortem investigations brain tissue from normal individuals and psychiatric patients.
In Specific Aim 1, the neurochemical profile of AMYG neurons projecting to L-THAL will be investigated.
In Specific Aim 2, the afferences from ACG to AMYG are examined with respect to the hypothesis that specific AMYG intemeuronal subtypes and a subpopulation of AMYG neurons projecting to L-THAL, may be the main target of these projections.
Specific Aim 3 is designed to test the hypothesis that mesoamygdaloid dopaminergic projections may contact AMYG neurons projecting to L-THAL.
In Specific Aim 4, the distribution of specific neurochemical markers investigated in Specific Aims 1-3 will be characterized in human AMYG. These studies are an integral part of a broader research plan in which postmortem investigations and a 'partial' rodent model are being used to investigate the role played by these brain regions in the pathophysiological mechanisms of schizophrenia. Within this context, the proposed studies will provide baseline information essential to the understanding of how a disruption of GABAergic transmission in ACG and AMYG might affect circuit functions linking these two regions among each other, to L-THAL and to the dopaminergic system. More in general, results obtained from the investigations described in this proposal will be relevant to the study of the physiological functions of AMYG and of its role in major psychiatric diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH066955-02
Application #
6766809
Study Section
Special Emphasis Panel (ZRG1-BDCN-2 (01))
Program Officer
Quinn, Kevin J
Project Start
2003-07-01
Project End
2008-04-30
Budget Start
2004-07-01
Budget End
2005-04-30
Support Year
2
Fiscal Year
2004
Total Cost
$177,750
Indirect Cost
Name
Mc Lean Hospital (Belmont, MA)
Department
Type
DUNS #
046514535
City
Belmont
State
MA
Country
United States
Zip Code
02478
Chelini, Gabriele; Pantazopoulos, Harry; Durning, Peter et al. (2018) The tetrapartite synapse: a key concept in the pathophysiology of schizophrenia. Eur Psychiatry 50:60-69
Markota, Matej; Sin, Jessica; Pantazopoulos, Harry et al. (2014) Reduced dopamine transporter expression in the amygdala of subjects diagnosed with schizophrenia. Schizophr Bull 40:984-91
Pantazopoulos, Harry; Woo, Tsung-Ung W; Lim, Maribel P et al. (2010) Extracellular matrix-glial abnormalities in the amygdala and entorhinal cortex of subjects diagnosed with schizophrenia. Arch Gen Psychiatry 67:155-66
Pantazopoulos, Harry; Murray, Elisabeth A; Berretta, Sabina (2008) Total number, distribution, and phenotype of cells expressing chondroitin sulfate proteoglycans in the normal human amygdala. Brain Res 1207:84-95
Pantazopoulos, Harry; Lange, Nicholas; Baldessarini, Ross J et al. (2007) Parvalbumin neurons in the entorhinal cortex of subjects diagnosed with bipolar disorder or schizophrenia. Biol Psychiatry 61:640-52
Pantazopoulos, Harry; Lange, Nicholas; Hassinger, Linda et al. (2006) Subpopulations of neurons expressing parvalbumin in the human amygdala. J Comp Neurol 496:706-22
Berretta, S; Pantazopoulos, H; Caldera, M et al. (2005) Infralimbic cortex activation increases c-Fos expression in intercalated neurons of the amygdala. Neuroscience 132:943-53