Cortical PV and VIP neurons are necessary for texture discrimination performance of freely behaving mice

by Aybeniz Ece Cetin
Doctoral thesis
Date of Examination:2025-03-20
Date of issue:2025-03-27
Advisor:Prof. Dr. Jochen F. Staiger
Referee:Prof. Dr. Jochen F. Staiger
Referee:Prof. Dr. Hansjörg Scherberger
Persistent Address: http://dx.doi.org/10.53846/goediss-11173

 

 

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Abstract

English

Rodents gather information about their surroundings through their whiskers, enabling them to differentiate textures, recognize objects, and navigate. Each whisker is represented in the barrel cortex (S1BF) by a single cortical column in an isomorphic manner. The microcircuits within each barrel-related column comprise both excitatory and inhibitory neurons. Extensive literature exists on genetically defined GABAergic neurons—parvalbumin (PV), vasoactive intestinal polypeptide (VIP), and somatostatin (SST)—and their involvement in tactile perception through whisking, including both passive stimulation of the whiskers and active touch. S1BF is well established as the core node for whisker-based texture discrimination. However, how PV, VIP, and SST interneurons contribute to the behavioral outcome of information processing during tactile perception in texture discrimination remains unclear. This study aims to further investigate the role of PV and VIP neurons in S1BF through chemogenetic activation in awake, freely behaving mice trained in a texture discrimination task. For this purpose, a novel whisker-based texture discrimination paradigm, the textured T-maze (TT), was developed, allowing mice to explore the maze freely while being trained on texture discrimination. PV-cre and VIP-cre mice exhibited comparable baseline performance. An activating Cre-dependent chemogenetic virus was bilaterally injected into the S1BF of PV-cre and VIP-cre mice to express “activating” DREADDs, enabling selective manipulation of PV and VIP cells via intraperitoneal administration of clozapine-N-oxide (CNO). Chemogenetic activation of either PV or VIP neurons impaired texture discrimination, reducing performance to chance level. Whole-cell patch-clamp experiments demonstrated that the intrinsic properties of transfected cells were comparable to those of non-transfected counterparts. The depolarizing effect of CNO on transfected cells was tested via bath application. Recordings confirmed that PV cells exhibited depolarization as expected from the viral construct, whereas VIP cells underwent depolarization block. In conclusion, although the chemogenetic virus did not produce equivalent depolarization effects in PV and VIP cells, the activation of PV cells or the putative deactivation of VIP cells in S1BF disrupted perceptual discrimination in freely behaving mice during the texture discrimination task.
Keywords: somatosensory cortex; vasoactive intestinal polypeptide; parvalbumin; tactile perception; whisking; chemogenetic manipulation
 
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