The overall goal of my research is to understand the mechanisms by which the activation of cortical inhibitory and excitatory circuits by incoming sensory information is modulated. The central hypothesis of this proposal is that presynaptic GABAB, adenosinc, and metabotropic glutamate receptors modulate thalamocortical stimulation of cortical inhibition. It is becoming increasingly clear that cortical inhibitory circuits play very important roles in sensory processing and cortical reorganization. Therefore, understanding how the activation of these inhibitory cortical circuits is regulated will provide important insights into how sensory processing can be altered pharmacologically. Perhaps in the future one would have the ability to alter sensory processing via receptor agonists or antagonists in order to assist in new skill learning, relearning after an accident or stroke, or treatment of conditions like phantom limb pain which have aberrant cortical reorganization. However, before any such interventions can be done we need more detailed information on the types and subtypes of receptors that regulate the activation of inhibitory cortical circuits via incoming sensory information. To begin to address; this deficit in our knowledge and extend the initial observations found during the first three years of this grant, the following aims are proposed.
Specific Aim 1 : To test the hypothesis that metabotropic glutamate receptors modulate thalamocortical excitation of inhibitory neurons.
Specific Aim 2 : To test the hypothesis that endogenously released GABA, adenosine. and glutamate can modulate thalamocortical excitation of inhibitory neurons.
Specific Aim 3 : To test the hypothesis that presynaptic GABAn, adenosine A1 and metabotropic glutamate receptors modulate thalamocortical stimulation in adult animals.
Specific Aim 4 : To test the hypothesis that intracortical and thalamocortical synapses are differentially reg,ulated by GABAB, adenosine and metabotropic glutamate receptors. Detailed knowledge of the pharmacology and physiology of the mechanisms which regulate the thalamic activation of cortical inhibitory circuits could improve treatments for people recovering from strokes or accidents.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Minority Biomedical Research Support - MBRS (S06)
Project #
5S06GM008239-23
Application #
7629039
Study Section
Minority Programs Review Committee (MPRC)
Project Start
Project End
Budget Start
2008-06-01
Budget End
2009-05-31
Support Year
23
Fiscal Year
2008
Total Cost
$338,890
Indirect Cost
Name
Ponce School of Medicine
Department
Type
DUNS #
105742043
City
Ponce
State
PR
Country
United States
Zip Code
00732
Diaz-Zabala, Hector J; Ortiz, Ana P; Garland, Lisa et al. (2018) A Recurrent BRCA2 Mutation Explains the Majority of Hereditary Breast and Ovarian Cancer Syndrome Cases in Puerto Rico. Cancers (Basel) 10:
Cuevas, Marielly; Cruz, Myrella L; Ramirez, Antonio E et al. (2018) Stress During Development of Experimental Endometriosis Influences Nerve Growth and Disease Progression. Reprod Sci 25:347-357
Encarnación, Jarline; Ortiz, Carmen; Vergne, Ralphdy et al. (2016) High DRC Levels Are Associated with Let-7b Overexpression in Women with Breast Cancer. Int J Mol Sci 17:
Matta, Jaime; Morales, Luisa; Ortiz, Carmen et al. (2016) Estrogen Receptor Expression Is Associated with DNA Repair Capacity in Breast Cancer. PLoS One 11:e0152422
Pérez, Wanda I; Soto, Yarelys; Ortíz, Carmen et al. (2015) Ferrocenes as potential chemotherapeutic drugs: synthesis, cytotoxic activity, reactive oxygen species production and micronucleus assay. Bioorg Med Chem 23:471-9
Mateo, Z; Porter, J T (2015) Developmental decline in modulation of glutamatergic synapses in layer IV of the barrel cortex by group II metabotropic glutamate receptors. Neuroscience 290:41-8
Fourquet, Jessica; Sinaii, Ninet; Stratton, Pamela et al. (2015) Characteristics of women with endometriosis from the USA and Puerto Rico. J Endometr Pelvic Pain Disord 7:129-135
Ruiz, Lynnette A; Báez-Vega, Perla M; Ruiz, Abigail et al. (2015) Dysregulation of Lysyl Oxidase Expression in Lesions and Endometrium of Women With Endometriosis. Reprod Sci 22:1496-508
Quiñones, Maria; Urrutia, Rebecca; Torres-Reverón, Annelyn et al. (2015) Anxiety, coping skills and hypothalamus-pituitary-adrenal (HPA) axis in patients with endometriosis. J Reprod Biol Health 3:
Matos-Ocasio, Félix; Hernández-López, Anixa; Thompson, Kenira J (2014) Ceftriaxone, a GLT-1 transporter activator, disrupts hippocampal learning in rats. Pharmacol Biochem Behav 122:118-21

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