Submedius thalamic inputs shape the presynaptic architecture of layer 5 orbitofrontal cortex in mice

Area of Science:

• Neuroscience
• Cognitive Neuroscience
• Behavioral Neuroscience

Background:

• The orbitofrontal cortex (OFC) is crucial for complex cognitive and social functions.
• Understanding the OFC's presynaptic inputs is vital for elucidating its role in behavior.
• The OFC's influence on maternal care in female mice is experience-dependent.

Purpose of the Study:

• To identify major presynaptic partners of the OFC, particularly inputs to layer 5 excitatory neurons.
• To characterize the functional connectivity between the submedius thalamus (SMT) and the OFC.
• To investigate the role of SMT in modulating OFC activity during maternal behavior.

Main Methods:

• Utilized trans-synaptic tracing to map inputs to OFC layer 5 neurons.
• Generated a novel mouse line (Tnnt1-Cre) for selective targeting of thalamic nuclei.
• Employed microendoscopic calcium imaging and projection-specific chemogenetic silencing.

Main Results:

• Identified the SMT and mediodorsal thalamus (MD) as major inputs to OFC layer 5 neurons.
• Revealed complementary projection patterns of SMT and MD within prefrontal regions.
• Observed pup retrieval-related activity and learning plasticity in the SMT, which modulates OFC activity.

Conclusions:

• The SMT is a significant, previously understudied thalamic input to the OFC.
• This study provides a presynaptic map of OFC layer 5 neurons.
• Demonstrated the feasibility of selectively manipulating SMT for studying OFC function in social behaviors.