Cell-type-specific control of basolateral amygdala neuronal circuits via entorhinal cortex-driven feedforward inhibition.

E Mae Guthman,Diego Restrepo,Philip Chu,Joshua D Garcia,Molly M Huntsman,Katharine R Smith,Ming Ma,Serapio M Baca

doi:10.7554/elife.50601

E Mae Guthman, Diego Restrepo + Show 6 more

Open Access

https://doi.org/10.7554/elife.50601

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Journal: eLife	Publication Date: Jan 9, 2020
Citations: 17	License type: CC BY 4.0

Affiliation: University of Colorado Anschutz Medical Campus

Abstract

The basolateral amygdala (BLA) plays a vital role in associating sensory stimuli with salient valence information. Excitatory principal neurons (PNs) undergo plastic changes to encode this association; however, local BLA inhibitory interneurons (INs) gate PN plasticity via feedforward inhibition (FFI). Despite literature implicating parvalbumin expressing (PV+) INs in FFI in cortex and hippocampus, prior anatomical experiments in BLA implicate somatostatin expressing (Sst+) INs. The lateral entorhinal cortex (LEC) projects to BLA where it drives FFI. In the present study, we explored the role of interneurons in this circuit. Using mice, we combined patch clamp electrophysiology, chemogenetics, unsupervised cluster analysis, and predictive modeling and found that a previously unreported subpopulation of fast-spiking Sst+ INs mediate LEC→BLA FFI.

Highlights

The ability of animals to learn to associate sensory stimuli with outcomes plays an important role in their survival
fast spiking (FS) Sst+ INs have a lower threshold stimulation intensity compared to PV+ INs, and FS Sst+ INs have greater subthreshold EPSP amplitudes and are more likely to fire in response to principal neurons (PNs) threshold stimulation of lateral entorhinal cortex (LEC) compared to PV+ INs. These findings suggest that LEC afferents to basolateral amygdala (BLA) have a greater functional convergence onto FS Sst+ INs compared to PV+ INs and raise the question whether they are involved in BLA FFI
LEC afferents synapsed onto both PV+ and FS Sst+ INs (Figures 2 and 3), only FS Sst+ INs fired in response to LEC activity (Figure 4); PV+ INs received stronger synaptic input from local BLA PNs than both populations of Sst+ INs

Summary

Introduction

The ability of animals to learn to associate sensory stimuli with outcomes plays an important role in their survival. After a few trials BLA neurons fire selectively to novel odors that are informative about the outcome in an associative olfactory learning task (Schoenbaum et al, 1999) This plasticity is critically important as future presentations of the stimulus can elicit robust firing in subsets of BLA PNs that output to downstream regions to guide goal-directed behavior (Beyeler et al, 2016; Janak and Tye, 2015; Quirk et al, 1995). It is these deep layer LEC neurons that innervate the BLA (McDonald, 1998; McDonald and Mascagni, 1997) Taken together, this raises the possibility that the LECfiBLA circuit could be involved in sensory-valence learning across sensory modalities or for more multimodal natural stimulus information under hippocampal influence. We tested this hypothesis by pairing patch clamp recordings in BLA with unsupervised cluster analysis, predictive modeling, and chemogenetic manipulations and found that a previously unreported subpopulation of fast spiking (FS) Sst+ INs mediate FFI in the LECfiBLA circuit

Results

Discussion

Materials and methods