Date of Award

Fall 2015

Project Type

Dissertation

Program or Major

Psychology

Degree Name

Doctor of Philosophy

First Advisor

Robert G Mair

Second Advisor

Robert C Drugan

Third Advisor

Brett M Gibson

Abstract

Medial thalamus has reciprocal connections with prefrontal cortex (PFC) that are thought to coordinate its activity with other areas of the telencephalon that support flexible goal-directed behavior. The mediodorsal nucleus is the primary source of specific thalamo-cortical projections to middle layers of PFC while midline and intralaminar nuclei provide modulatory inputs to deep and superficial layers of PFC and to anatomically-related areas of the basal ganglia and hippocampus. Each of these nuclei receive direct cortico-thalamic and indirect cortico- striato-pallidal input from PFC. Medial thalamic lesions impair flexible goal-directed behavior, exemplified by delayed non-matching to position tasks (DNMTP).

To elucidate the influence of medial thalamus on PFC function we examined the effects of temporary thalamic inactivation on the response properties of prefrontal neurons in rats performing a dynamic DNMTP task. Cellular activity was recorded throughout medial PFC using a drivable array of tetrodes. Electrophysiological recordings were analyzed offline to identify signals from isolated neurons and to correlate activity with specific behavioral events as rasters and peri-event time histograms (PETH).

Once cells with significant behavioral correlations (PETH responses beyond 99% confidence interval) were identified (day 1), the tetrode array was left in place for two more sessions. On the next day (day 2), central thalamus was unilaterally inactivated using microinjections of the GABAA agonist muscimol. On day 3, activity in the same location was recorded again without thalamic inactivation. We used doses of muscimol previously shown to impair delayed matching to position when injected bilaterally at the same site. Unilateral inactivation had no significant effect on DNMTP performance.

Examination of waveforms, inter-spike-interval histograms, cluster analyses, and event related activity (on days 1 and 3) confirmed the identity of single neurons across the three days. Day 2, inactivation was consistently associated with significant disruption of event-related activity of prefrontal neurons, but not with significant changes in performance accuracy or mean firing rate of cells. Some neurons exhibited increased and others and decreased levels of activity, suggesting both inhibitory and excitatory modulation of PFC by thalamus. These data indicate a critical role for medial thalamus in shaping the activity of cortical neurons in relation to memory dependent responding and goal directed action.

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