Biology subjects

Tan, K. R.

Publications and source records attributed to Tan, K. R..

3 recordsLinked to original sources

bioRxiv2021

GABAB receptor/HCN channel complexes in VTA dopamine neurons limit synaptic inhibition and prevent anxiety-like behavior

Aversive stimuli inhibiting dopamine neurons in the ventral tegmental area (DAVTA neurons) induce anxiety-like behaviors. The inhibition of DAVTA neurons is prolonged by GABAB receptor (GBR)-activated K+-currents, which exhibit a rapid desensitization of unknown physiological relevance. We now report that GBRs associate via auxiliary KCTD16 subunits with HCN channels, which facilitates activation of hyperpolarization- activated currents (Ih) by GBR-activated K+ currents. Activation of Ih underlies rapid K+ current desensitization in DAVTA neurons and limits GBR-mediated inhibition. Disruption of the GBR/HCN complex in KCTD16-/- mice or blockade of Ih prolongs optogenetically driven inhibition of DAVTA neuron firing. KCTD16-/- mice exhibit an increased anxiety-like behavior in response to stressful stimuli, which is reproduced by in vivo CRISPR/Cas9-mediated KCTD16 ablation in DAVTA neurons or intra-VTA infusion of HCN antagonist to wild-type mice. Our data reveal that GBR-induced Ih protect DAVTA neurons from prolonged GBR- mediated inhibition in response to stressors, which moderates anxiety-like behaviors.

neuroscience↗

bioRxiv2020

Zona Incerta subpopulations differentially encode and modulate anxiety

Despite recent clinical observations linking the Zona Incerta (ZI) to anxiety, little is known about whether and how the ZI processes anxiety. Here, we subject mice to anxious experiences and observe an increase in ZI cfos-labelled neurons and single-cell calcium activity as well as an efficient effect of ZI infusion of diazepam a classical anxiolytic drug. We further identify that somatostatin-(SOM), calretinin-(CR), and vesicular glutamate transporter-2 (Vglut2)-expressing cells display unique electrophysiological profiles; yet they similarly respond to anxiety-provoking stimuli and to diazepam. Interestingly, optogenetic manipulations reveals that each of these ZI neuronal population triggers specific anxiety-related behavioral phenotypes. Activation of SOM-expressing neurons induced anxiety while in stark contrast, photo-activation of CR-positive cells and photo-inhibition of Vglut2-expressing neurons produce anxiolysis. Furthermore, activation of CR- and Vglut2-positive cells provokes rearing and jumps; respectively. Our findings provide the first experimental evidence that ZI subpopulations encode and modulate different components of anxiety.

neuroscience↗

bioRxiv2020

Midbrain modulation of conditioned learning

The firing activity of striatal cholinergic interneurons (CINs) is a neural correlate of conditioned learning. However, its circuitry is not entirely described. Here we report that midbrain GABA and Glutamate neurons discriminate auditory cues and encode the association of a predictive stimulus with a footshock. Through their mono- and di-synaptic inputs via the thalamic-parafasicular sub-nucleus onto CINs, they contribute to processing fear learning.

neuroscience↗