Biology subjects

Kochubey, O.

Publications and source records attributed to Kochubey, O..

5 recordsLinked to original sources

bioRxiv2025

CS - plasticity and behavioral-state integration in the posterior insula during auditory fear learning

During fear learning, animals learn to associate sensory cues (conditioned stimulus, CS) with aversive outcomes, and neurons in several brain areas become entrained to the CS. The posterior insular cortex (pInsCx) contains representations of internal states and sensory cues, amongst them auditory stimuli. Nevertheless, the possibility of plastic encoding of auditory responses in the pInsCx during fear learning, and its underlying synaptic mechanisms have not been addressed. Using single-unit recordings in the pInsCx of male mice during fear learning, we find that [~] 10% of putative principal neurons acquire a response to an auditory CS during fear learning ("CS learners"). CS learners are enriched in the insula auditory field (IAF) of the dorsal pInsCx, and strongly overlap with a larger neuronal subpopulation which increases its activity during movement initiation. Using optogenetic circuit mapping, we find that the IAF receives glutamatergic synapses from the non-lemniscal auditory thalamus and the auditory cortex (A1); fear learning induces a postsynaptic form of LTP at the cortical, but not at the thalamic input synapse. Combined single-unit recordings and optogenetic axon silencing showed that the acquired CS-response during fear recall depends on transmission at the A1 [->] pInsCx synapse. Our study shows that the pInsCx generates a plastic representation of an auditory CS during fear learning, driven by LTP of an associative cortical input. Future work should further investigate how the integration of CS- and movement information in the insula contributes to the expression of auditory-cued fear memories.

neuroscience↗

bioRxiv2023

An insular cortex to lateral amygdala pathway in fear learning

During fear learning, associations between an aversive stimulus (the US), and a sensory cue (CS) are formed at specific brain synapses. Nevertheless, how US information is transmitted to brain areas involved in value processing, like the amygdala, is still elusive. Using optogenetics, in-vivo Ca2+ imaging, and circuit tracing, we investigate the role of the posterior insular cortex (pInsCx) and relevant output pathways of this cortical area in fear learning. Optogenetic suppression of US-signaling in pInsCx principal neurons compromises auditory-cued fear learning. The pInsCx makes a robust glutamatergic synapse in the lateral amygdala (LA), which undergoes long-term potentiation after fear learning, and transmits US-information to a sub-population of LA neurons. Suppressing US-signaling in LA-projectors recapitulates the fear learning deficits observed after silencing pInsCx principal neurons. Thus, the pInsCx, via a plastic output synapse, transmits US-information to the LA and critically contributes to the formation of auditory-cued fear memories.

neuroscience↗

bioRxiv2021

A striatal circuit balances learned fear in the presence and absence of sensory cues

During fear learning, defensive behaviors like freezing need to be finely balanced in the presence or absence of threat-predicting cues (conditioned stimulus, CS). Nevertheless, the circuits underlying such balancing are largely unknown. Here, we investigate the role of the ventral tail striatum (vTS) in auditory-cued fear learning of male mice. In-vivo Ca2+ imaging showed that robust sub- populations of direct (D1R+) and indirect pathway neurons (Adora+) in the vTS responded to footshocks, and to the initiation of movements after freezing; moreover, a sub-population of D1R+ neurons increased its responsiveness to an auditory CS during fear learning. In-vivo optogenetic silencing shows that footshock-driven activity of D1R+ neurons contributes to fear memory formation, whereas Adora+ neurons modulate freezing in the absence of a learned CS. Circuit tracing identified the posterior insular cortex (pInsCx) as an important cortical input to the vTS, and recording of optogenetically-evoked EPSCs revealed long-term plasticity with opposite outcomes at the cortical synapses onto D1R+ - and Adora+ neurons. Thus, direct- and indirect pathways neurons of the vTS show differential signs of plasticity after fear learning, and balance defensive behaviors in the presence and absence of learned sensory cues.

neuroscience↗

bioRxiv2021

Optogenetic stimulation of medial amygdala GABA neurons with kinetically different channelrhodopsin variants yield opposite behavioral outcomes

Optogenetic manipulation of genetically-specified neuron populations has become a key tool in circuit neuroscience. The medial amygdala (MeA) receives pheromone information about conspecifics and has crucial functions in social behaviors; interestingly, this amygdalar structure contains a majority of GABAergic projection neurons. A previous study showed that optogenetic activation of MeA GABA neurons with channelrhodopsin-2H134R (ChR2) strongly enhanced inter-male aggression (Hong et al. 2014, Cell). When we attempted to reproduce these findings, accidentally using a faster channelrhodopsin variant (channelrhodopsin-2H134R,E123T or ChETA), we found the opposite results. We therefore systematically compared the behavioral outcome of optogenetic stimulation of MeApd GABA neurons with ChETA versus ChR2, employing two widely used AAV serotypes. This revealed that optogenetic stimulation with ChETA suppressed aggression, whereas optogenetic stimulation with ChR2 increased aggression. Recordings of membrane potential changes following optogenetic stimulation with ChETA versus ChR2 revealed larger plateau depolarizations, smaller action potential amplitudes, and larger local inhibition of neighboring inhibitory neurons with ChR2 as compared to ChETA. Our study shows that channelrhodopsin variants have to be chosen with care for in-vivo optogenetic experiments. Furthermore, the role of MeApd GABA neurons in aggression control should be re- evaluated.

neuroscience↗

bioRxiv2019

Dopamine in the basal amygdala signals salient somatosensory events during fear learning

The amygdala is a brain area critical for the formation of threat memories. However, the nature of the teaching signal(s) that drive plasticity in the amygdala are still under debate. Here, we use optogenetic methods to investigate whether dopamine release in the amygdala contributes to fear learning. Antero- and retrograde labeling showed that a sparse, and relatively evenly distributed population of ventral tegmental area (VTA) neurons projects to the basal amygdala (BA). In-vivo optrode recordings in behaving mice showed that many VTA neurons, amongst them putative dopamine neurons, are excited by footshocks. Correspondingly, in-vivo fiber photometry of dopamine in the BA revealed robust dopamine concentration transients upon footshock presentation. Finally, silencing VTA dopamine neurons, or their axon terminals in the BA during the footshock, reduced the extent of threat memory retrieval one day later. Thus, VTA dopamine neurons projecting to the BA code for the saliency of the footshock event, and the resulting dopamine release in the BA facilitates threat memory formation.

neuroscience↗