| Abstract No.: | B-E2169 |
| Country: | Canada |
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| Title: | POSSIBLE INVOLVEMENT OF INTERHEMISPHERIC CALLOSAL PROJECTION NEURONS IN THE MEDIAL PREFRONTAL CORTICAL GLUTAMATE RESPONSE TO STRESS. |
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| Authors/Affiliations: | 1 Derek Lupinsky*; 1 Luc Moquin; 1 Alain Gratton;
1 Douglas Mental Health University Institute, Montreal, QC, Canada
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| Content: | Stress activates ventral tegmental area (VTA) dopamine (DA) neurons that project to the medial prefrontal cortex (mPFC). In addition to causing robust increases in PFC DA, stress will also elevate PFC glutamate (GLU) levels. The PFC receives GLU-containing inputs from several extra-cortical regions (e.g. hippocampus, amygdala, and thalamus). In the present study, we explored the possibility that the PFC GLU stress response reflects activation of callosal projection neurons originating in the opposite PFC. Some pyramidal GLU-containing PFC neurons are known to project to the opposite PFC where they terminate primarily onto pyramidal neurons but also on gamma-aminobutyric acid (GABA) neurons and interneurons. Both callosal neurons and GABA interneurons appear to be DA-sensitive such that their activity is altered in a complex manner by stress-induced changes in DA transmission. Significant hemispheric asymmetries in the PFC DA stress response as well as evidence that neuroendocrine and autonomic responses to stress are differentially altered by left versus right PFC lesions suggest a possible involvement of such interhemispheric projection neurons. To address this possibility, we studied the effects of unilateral PFC lesions and central drug injections on contralateral PFC GLUT efflux. Freely-moving, adult male Long Evans rats were subjected to microdialysis procedures whereby a probe with a 3mm active tip was inserted into the PFC. Dialysate samples were collected every 10 minutes for 1 hour prior to, during and after a 20 minute period of tail-pinch stress. Samples were immediately analysed using pre-column derivatization and high performance liquid chromatography with electrochemical detection (HPLC-EC). GLU activity during 20 minutes of stress was 130-140% greater than pre-and-post stress levels; however, the magnitude of the increase was not hemisphere dependent. Reverse dialysis of TTX (1µM) dampened stress-induced GLU release such that GLU activity was indistinguishable from pre-or-post stress levels. Compared to sham controls, excitotoxic lesions of the left or right infralimbic (IL) and prelimbic (PL) PFC abolished stress-induced GLU activity in the opposite hemisphere. Central administration of LY379268 prior to stress strongly decreased contralateral stress-induced GLU efflux to levels significantly below baseline activity. Using the D-1 receptor antagonist, SCH23390, D-1 antagonism of the left or right IL-PFC enhanced contralateral stress-induced GLU. Right-side, post-stress GLU activity was comparatively elevated for the remainder of the session when SCH23390 was injected into the left IL-PFC. These findings provide evidence that the PFC GLU response to stress is modulated by mechanisms in the opposite PFC. The most obvious candidate mediating this effect comprises interhemispheric callosal pyramidal projection neurons. The present findings raise the possibility that disruption or modulation of PFC interhemispheric GLU communication might contribute to maladaptive stress responsivity associated with abnormal lateralization of cortically-mediated function. |
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