Functional architecture of the mediodorsal thalamus

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.

Grant Number: 5R01MH131857-03
NIH Institute/Center: NIH
Principal Investigator: Audrey Brumback