The entorhinal cortical alvear pathway differentially excites interneuron subtypes in hippocampal CA1

Abstract

The entorhinal cortex alvear pathway is a major excitatory input to hippocampal CA1, yet nothing is known about its physiological impact. We investigated the alvear pathway projection and innervation of neurons in CA1 using optogenetics and whole cell patch clamp methods in transgenic mouse brain slices. Using this approach, we show that the medial entorhinal cortical alvear inputs onto both CA1 pyramidal cells and stratum oriens interneurons were monosynaptic, had low release probability, and were mediated by AMPA receptors. Optogenetic theta burst stimulation was unable to elicit suprathreshold activation of CA1 pyramidal neurons but was capable of activating CA1 stratum oriens interneurons. CA1 stratum oriens interneuron subtypes were not equally affected. Higher burst action potential frequencies were observed in parvalbumin-expressing interneurons relative to vasoactive-intestinal peptide-expressing or a subset of oriens lacunosum-moleculare interneurons. Furthermore, alvear excitatory synaptic responses were observed in greater than 70% of PV and VIP interneurons and less than 20% of O-LM cells. Finally, greater than 50% of theta burst-driven inhibitory postsynaptic current amplitudes in CA1 PCs were inhibited by optogenetic suppression of PV interneurons. Therefore, our data suggest that the alvear pathway primarily affects hippocampal CA1 function through feedforward inhibition of select interneuron subtypes.