Anterior thalamic glutamatergic neurons modulate prefrontal cortical firing and regularity

For decades, studies on learning and memory focused extensively on the neural circuitry between the hippocampus and the prefrontal cortex, with minimal consideration of the role of the anterior thalamic nucleus (ATN). The diencephalic nucleus is rich in excitatory glutamate neurons that project to both the hippocampus and medial prefrontal cortex (mPFC). Neural projections from the hippocampus and mPFC have also been identified in the ATN through reciprocal circuits. Although ATN lesioning leads to memory loss (amnesia), the role of the ATN in the propagation of cognitive processes in the mPFC is still poorly understood. In the current study, we employed adeno-associated viral labeling and in vivo electrophysiology to trace ATN glutamate neural projections in the layers of the mPFC. Neuroanatomical mapping of ATN Vglut2⁺ projections revealed a topographic gradient in the infralimbic cortex (IL), prelimbic cortex (PrL), and cingulate cortex (Cg1). Specifically, the IL has the least ATN Vglut2⁺ terminals while the PrL (layer III) and Cg1 (layers III, Va/b, VI) have robust innervation. Functional tracing of the thalamocortical projection was performed by combining extracellular Cg1 and ATN recording with ATN Vglut2⁺ neuron photostimulation. Our results show that light-activated ATN Vglut2⁺ neurons drive Cg1 neural activity and increase the firing rate of putative pyramidal neurons in anesthetized mice. In addition, Cg1 putative neurons that were activated during ATN photostimulation show a significant increase in firing regularity in comparison with the baseline (no ATN stimulus). Together, our results show that ATN Vglut2⁺ neurons modulate the firing rate and regularity of the putative Cg1 pyramidal cells, thus, creating a premise for direct influence on cognitive processes in cortical networks.