# An investigation of the nature of the anatomical connectivity between medial prefrontal cortex and caudate-putamen reward sites in the rat.

 Title: An investigation of the nature of the anatomical connectivity between medial prefrontal cortex and caudate-putamen reward sites in the rat. Author: Trzcinska, Monika Maria. Abstract: Research on the mechanisms by which the brain codes, understands, and remembers reward has focused on sites lying along the medial forebrain bundle (MFB). Regions more anterior to the MFB, such as the medial prefrontal cortex (MPFC) and caudate-putamen (CPu), have received little attention in this regard. Consequently, the first experiment was to determine the distribution of sites in the MPFC and CPu that support intracranial self-stimulation. Overall, 255 MPFC and 187 CPu individual sites were evaluated in 67 animals using moveable electrodes; only 11% of the examined areas showed reliable self-stimulation, which was in most cases accompanied by overt seizures. Most positive sites were clustered in the ventromedial aspects of the MPFC and CPu. Charge values obtained for both regions were widely distributed and ranged from 0.68 to 1.63 $\mu$C across sites, values in line with those reported for MFB sites. One of the problems encountered in this study was the slow acquisition of MPFC self-stimulation. In order to overcome this obstacle, some subjects were implanted with two electrodes, one aimed at the MPFC, and the other at the CPu, ventral tegmental area, or lateral hypothalamus. Once stable thresholds were obtained at the extra MPFC sites, self-stimulation was then evaluated at the MPFC site. Only animals with CPu placements showed transference of this behaviour to the MPFC, suggesting that these two regions might form part of the same reward substrate, a view that has anatomical and electrophysiological support. The next step was to estimate the excitability cycles that characterize MPFC and CPu reward fibers. Using the behavioural adaptation of the refractory period test, the range of recovery from refractoriness was determined to span from 0.8 to 5.4 ms for the CPu and 1.4 to 7.9 ms for the MPFC. These values tend to be longer than the ones typically obtained at MFB self-stimulation sites. One interpretation of the overlap in these estimates is that these regions constitute two separate locations along the same axonal bundle. This hypothesis was investigated in the third experiment using the behavioural collision technique. Nine ipsilateral pairs of CPu and MPFC sites were evaluated for axonal connectivity, four of which showed a pattern consistent with the interpretation that at least a subset of fibers course between the MPFC and CPu. The conduction velocity estimates of these were calculated to be between 0.2 and 1.8 m/s, values that are much less than the estimates reported for the MFB and consistent with the activation of thin, unmyelinated axons. The anatomical relationship between the MPFC and CPu is characterized by direct corticostriatal projections, some of which use glutamate as a neurotransmitter. There is also some evidence that dopaminergic fibers make direct contact with these descending neurons. The behavioural estimates of refractoriness and the conduction velocities obtained here closely match those found electrophysiologically for dopaminergic and glutamatergic fibers. Given this background, a model of a possible neuronal interaction between the MPFC and CPu reward regions is proposed to account for the findings reported here, suggesting the involvement of these neurotransmitter systems in mediating the rewarding effects of MPFC and CPu stimulation. Date: 1995 URI: http://hdl.handle.net/10393/10347

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