Functional architecture of the mediodorsal thalamus

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PROJECT SUMMARY The mediodorsal thalamus (MD) and its reciprocal connection with medial prefrontal cortex (mPFC) control important aspects of executive functioning and social behavior. Dysfunction of this neural circuit can cause developmental brain disorders and neuropsychiatric conditions. Understanding prefrontal thalamocortical (MD→mPFC) circuit function has been hampered by a lack of understanding of MD projection neuron types and how they integrate and process synaptic information. The central hypothesis is that differences in intrinsic properties and connectivity between the two major populations of neurons that provide ascending input to the mPFC causes them to extract and transmit different information to the mPFC. Thus, these two populations have different roles in behavior. The overall goal is to expand understanding of the circuits within MD. The rationale is that understanding of neural processing by the thalamus and thalamic inputs to prefrontal cortex is necessary for understanding the mechanisms of executive function and developing neuromodulation therapies targeting the prefrontal network for neuropsychiatric disorders. The central hypothesis will be tested with three specific aims: 1) Determine how intrinsic properties of MD neurons control synaptic integration of mPFC inputs. 2) Test how MD neurons differentially process synaptic inputs arising from different brain regions. 3) Determine how optogenetic manipulation of specific MD circuits affects cognitive, social, and affective behaviors in wildtype mice. The research proposed in this application is innovative, in the applicant's opinion, because it defines the function of an understudied but essential thalamic nucleus, from the level of membrane biophysics, to synaptic integration, to control of behavior. The work is significant because it will contribute to the anatomical and physiological map of prefrontal thalamocortical circuitry. Ultimately, such knowledge has the potential to guide the development of future neuromodulation strategies to treat the symptoms of neuropsychiatric disorders that localize to the prefrontal network.