The mediodorsal (MD) and adjacent reuniens (Re) and intralaminar (IL) nuclei are prominent components of central thalamus that are organized to provide rapid and precise modulatory control of distributed neural networks involving medial prefrontal cortex (mPFC) that support adaptive goal-directed behavior. The essential role of these nuclei in cognition and awareness has been established by clinical and preclinical studies of neurological and psychiatric disorders that affect them. There is surprisingly little known about the activity of neurons in these nuclei and how they influence the networks they innervate during goal- directed behavior. We propose to address this gap in our knowledge by studying neuronal activity in rats performing dynamic delayed nonmatching to position (dDNMTP): a task that incorporates critical features of goal-directed behavior affected by mPFC, hippocampal, and central thalamic lesions. Preliminary studies were conducted to compare coding properties of neurons in MD and mPFC and to examine the effects of inactivating central thalamus on mPFC activity during dDNMTP. We propose to advance this work by conducting three new lines of investigation. The first will examine neuronal activity during task manipulations of dDNMTP designed to characterize differences in coding properties of neurons in MD, rostral and caudal IL, and Re. We want to learn how information is represented about actions, outcomes, and contextual factors that underlie behavioral choice. Our goal is to elucidate neuronal activity that underlies functions supported by individual nuclei in awake, behaving animals.
The second aim will use optogenetic methods to examine the effects of temporarily disrupting MD. MD will be disrupted unilaterally to preserve behavioral function and to allow contralateral mPFC to serve as a control for nonspecific effects of the treatment. We want to learn how MD contributes to the disruptive effects of central thalamic inactivation on neuronal coding in mPFC observed in preliminary studies and behavioral performance observed in earlier reports. Our goal is to understand how momentary changes in MD activity affect mPFC function.
The third aim will examine effects of unilateral MD lesions. We will lesion MD before dDNMTP training begins to deprive ipsilesion mPFC of MD input during learning. One control group will receive lesions after training (before recording begins) and another control group will receive sham surgery. We want to ascertain how MD affects neuronal responses in mPFC during learning and how chronic lesions affect the expression of mPFC responses for tasks learned before lesions are made. Our goal is to test the hypotheses that MD plays critical roles shaping responses of mPFC neurons during learning and optimizing information processing in mPFC once behaviors are learned. Beyond its scientific contributions this proposal will enrich opportunities for undergraduate and graduate neuroscience research at UNH providing research opportunities and funds to support students who might otherwise be unable to afford to commit the time required to participate fully in our research program.
The mediodorsal (MD) and adjacent midline and intralaminar thalamic nuclei play an essential role in cognition, providing fast and precise modulation of distributed neural networks. Aim 1 will define the nature of neuronal activity that gives rise to fast thalamic modulation. Aim 2 will examine effects of brief optogenetic disruption of MD and Aim 3 chronic effects of MD lesions on the learning and expression of prefrontal neuronal activity that underlies flexible, goal-directed behavior.
| Miller, Rikki L A; Francoeur, Miranda J; Gibson, Brett M et al. (2017) Mediodorsal Thalamic Neurons Mirror the Activity of Medial Prefrontal Neurons Responding to Movement and Reinforcement during a Dynamic DNMTP Task. eNeuro 4: |
