Parvalbumin interneuron mediated feedforward inhibition controls signal output in the deep layers of the perirhinal‐entorhinal cortex

Abstract

The perirhinal (PER) and lateral entorhinal (LEC) cortex form an anatomical link between the neocortex and the hippocampus. However, neocortical activity is transmitted through the PER and LEC to the hippocampus with a low probability, suggesting the involvement of the inhibitory network. This study explored the role of interneuron mediated inhibition, activated by electrical stimulation in the agranular insular cortex (AiP), in the deep layers of the PER and LEC. Activated synaptic input by AiP stimulation rarely evoked action potentials in the PER‐LEC deep layer excitatory principal neurons, most probably because the evoked synaptic response consisted of a small excitatory and large inhibitory conductance. Furthermore, parvalbumin positive (PV) interneurons—a subset of interneurons projecting onto the axo‐somatic region of principal neurons—received synaptic input earlier than principal neurons, suggesting recruitment of feedforward inhibition. This synaptic input in PV interneurons evoked varying trains of action potentials, explaining the fast rising, long lasting synaptic inhibition received by deep layer principal neurons. Altogether, the excitatory input from the AiP onto deep layer principal neurons is overruled by strong feedforward inhibition. PV interneurons, with their fast, extensive stimulus‐evoked firing, are able to deliver this fast evoked inhibition in principal neurons. This indicates an essential role for PV interneurons in the gating mechanism of the PER‐LEC network.

Distinct disease‐sensitive GABAergic neurons in the perirhinal cortex of Alzheimer's mice and patients

“…Therefore, the loss of PV cells in the perirhinal cortex might significantly contribute to AD‐related pathology in this vulnerable brain region. Besides inhibiting locally, PV neurons in the perirhinal cortex also project to the superficial layers of the entorhinal cortex, mediating a feedforward inhibition that controls the output signals connecting this region with the hippocampus . Therefore, a reduced activity in this GABAergic population could promote hyperactivity in the entorhinal cortex and, consequently, hyperexcitability across the hippocampus .…”

Decoding the porcine developing spatial processing system and production of human entorhinal stellate cell-like cells by a direct programming approach

“…Of these latter markers, PVALB has been particularly important for the identification of INs in the EC. Several references have reported PVALB+ INs and their inhibitory gradients in the EC (Beed et al, 2013;Fujimaru and Kosaka, 1996;Miao et al, 2017;Willems et al, 2018;Wouterlood et al, 1995). To confirm that PVALB was expressed at low levels during early gestation, we performed immunohistochemistry and detected moderate PVALB+ in the superficial layers from E100 ( Figure 7G) and onwards (P75) ( Figure S2A).…”

DNA Methyltransferase 1 (DNMT1) Function Is Implicated in the Age-Related Loss of Cortical Interneurons

“…Fast-spiking parvalbumin (PV) positive interneurons represent the most abundant subset of cortical inhibitory interneurons (Druga, 2009). They execute both feedforward and feedback inhibition, and are responsible for generating gamma-frequency oscillations (Sohal et al, 2009;Buzsáki and Wang, 2012;Kann et al, 2014;Willems et al, 2018). In schizophrenia patients, a reduction in PV interneurons and their dysfunction have been associated with the loss of gamma oscillations, manifesting in working memory and executive function deficits (Torrey et al, 2005;Sohal et al, 2009).…”