17778
Intrinsic Excitability Defects in Specific Subtypes of Medial Prefrontal Cortex Pyramidal Neurons in a Mouse Model of Autism
Objectives: We hypothesize that in autism, the proposed pathological changes do not come about via global changes in the overall level of cortical excitation or inhibition, but rather reflect an imbalance of activity between these two subtypes of cortical pyramidal neurons.
Methods: We performed whole cell current clamp recordings from mPFC L5 Type A and B cells in acute brain slices from adult mice exposed to valproate or saline in utero at embryonic day 10.5.
Results: We found that in the prenatal valproate exposure mouse model of autism (“VPA mice”), there is a defect in action potential generation in the cortically projecting (Type B) mPFC neurons but not the subcortically projecting (Type A) cells. In addition, we found that in VPA mice, Type A but not Type B cells had decreased frequency of action potentials to injected current. By elucidating how these subtype-specific cellular alterations relate to synaptic, EEG, and behavioral abnormalities, our studies may lead to new ways of understanding neuronal circuit dysfunction in autism.
Conclusions: By elucidating how these subtype-specific cellular alterations relate to synaptic, EEG, and behavioral abnormalities, our studies may lead to new ways of understanding neuronal circuit dysfunction in autism.