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

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.

Hyperexcitability and Loss of Feedforward Inhibition Contribute to Aberrant Plasticity in theFmr1KO Amygdala

“…Future studies should address the idiosyncrasies of how loss of Fmr1 affects distinct neural circuits across the brain and their corresponding behaviors. Converging evidence from our group and others implicates LA Sst + INs in FFI gating of LTP ( Smith et al, 2000 ; Bissière et al, 2003 ; Unal et al, 2014 ; Wolff et al, 2014 ; Ito et al, 2019 ; Guthman et al, 2020 ). However, it remains to be shown if specific alterations in Sst + IN function underlie the facilitated LTP seen in Frm1 KO LA.…”

“…The local circuit INs play an important role regulating the synaptic plasticity underlying this in vivo learning process ( Bissière et al, 2003 ; Wolff et al, 2014 ). Our group and others have shown this inhibitory control is exerted via a feedforward circuit motif from somatostatin-expressing (Sst) INs which modulates long-term potentiation (LTP) at cortical and thalamic afferent synapses onto BLA PNs ( Smith et al, 2000 ; Bissière et al, 2003 ; Tully et al, 2007 ; Unal et al, 2014 ; Wolff et al, 2014 ; Bazelot et al, 2015 ; Ito et al, 2019 ; Guthman et al, 2020 ). Thus, feedforward inhibition (FFI)-gated LTP is an underlying circuit mechanism for the acquisition of threat conditioning.…”

Brain‐wide mapping of presynaptic inputs to basolateral amygdala neurons

“…The amygdala plays crucial roles in emotional memory and motivated behavior (Janak & Tye, 2015; LeDoux, 2000). There have been numerous studies on the anatomical and functional connectivity of the amygdala (Adhikari et al, 2015; Carlsen et al, 1985; Dalmay et al, 2019; Do‐Monte et al, 2017; Guthman et al, 2020; Hasegawa et al, 2017; Kim & Cho, 2017a, b; Lang & Pare, 1997; Li et al, 1996; Mascagni et al, 1993; McCall et al, 2017; McDonald, 1998; Nickerson Poulin et al, 2006; Romanski & LeDoux, 1993; Senn et al, 2014; Vertes & Hoover, 2008; Woodson et al, 2000; Yu et al, 2017). Although the major sources of input to BLA neurons have been identified, the input and output anatomical organization of the BLA neural circuit is not clear.…”

Interneuron Types and Their Circuits in the Basolateral Amygdala

“…SST interneurons are also part of inhibitory circuits in the BLA, as they innervate and are targeted by both PV and VIP interneurons (Krabbe et al, 2019 ). In addition to SST interneurons displaying accommodating firing and sag in their voltage responses upon negative step current injections, many SST interneurons showing rather a fast-spiking phenotype and no sag were sampled in transgenic mice generated by crossing Sst-Cre mice with a reporter mouse line (Guthman et al, 2020 ; Unal et al, 2020 ). Interestingly, such fast-spiking interneurons were rarely found among SST interneurons if they were visualized by a viral strategy in Sst-Cre mice (2 out of 31; Vereczki et al, 2021 ).…”