The role of the claustrum during eyeblink conditioning

  1. Maria Del Mar Reus Garcia
Dirixida por:
  1. José María Delgado García Director

Universidade de defensa: Universidad Pablo de Olavide

Ano de defensa: 2021

Tribunal:
  1. Gilad Silberberg Presidente/a
  2. Rocío Leal Campanario Secretaria
  3. Juana Gallar Martinez Vogal

Tipo: Tese

Teseo: 654193 DIALNET lock_openTESEO editor

Resumo

The claustrum (CL) is a sheet-shaped grey matter structure hidden beneath the inner surface of the neocortex and located between the putamen and the insular cortex. It is present in all mammals, and also birds and reptiles have a homologous structure. When first described, a century ago, it was thought to be a mere relay station given its dense, reciprocal connections to the rest of the brain. Nowadays, thanks to the great effort of a growing number of scientists, we know it is related to attentional processes, salience detention, multisensory integration, brain oscillation synchrony, and even learning and memory consolidation during sleep. It has also been proved that CL cells can respond to single sensorial stimuli, particularly when they involve novelty or alertness, although more research will be needed to elucidate the CL function. Given these outstanding characteristics, the present Doctoral Thesis focuses on assessing the involvement of claustral neurons during associative learning, specifically in classical eyeblink conditioning, in rabbits. A simple delay paradigm was used: a 350 ms tone was presented as the conditioned stimulus (CS); 250 ms after the CS onset, a 100 ms air puff aimed at the eye was used as the unconditioned stimulus (US); thus CS and US co-terminated. Electromyographic recordings of the activity of the orbicularis oculi muscle were used to monitor the learning progress. The contraction of this muscle during the 250 ms after the CS onset was considered a conditioned response (CR) and was learning-dependent; if the movement happened in the 100 ms after the US onset or later, it was considered a reflex or unconditioned response (UR) and was unrelated to learning. To achieve our purpose, we firstly attained electrophysiological extracellular single-unit recordings from the activity of CL neurons during eyeblink conditioning. CL neurons were located by synaptic and/or antidromic activation from motor (MC), medial prefrontal (mPFC), and cingulate cortices (CC). Secondly, the local field potentials (LFPs) were recorded for CL, MC, and mPFC, also during eyeblink conditioning. As a last step, we used the vINSIST method to synaptically block the CL output before or after the acquisition of the conditioned eyeblinks. Single-unit recordings were analyzed from two habituation (only the CS was presented), eight conditioning (paired CS/US), and six pseudoconditioning sessions (unpaired CS and US). During habituation and pseudoconditioning sessions, the activity of most recorded cells was rarely distorted by the unpaired CS or US. Remarkably, some CL neurons (type A) responded with a burst of activity after the paired CS/US presentation, especially during the acquisition phase of the conditioning. However, the activity of type A cells was not linearly related to the area of the CRs. In contraposition, type B neurons were inhibited after the CS/US. Firing pattern and spike duration analyses revealed that type A cells were projection neurons, while type B cells were interneurons. LFPs recorded in CL, MC, and mPFC changed their spectral powers across conditioning sessions for all the selected frequency bands. Moreover, significant delta-gamma comodulations were detected at CL-mPFC network nodes during certain conditioning phases. Finally, inactivation of CL synaptic connectivity affected the number and the amplitude of CRs across the conditioning, but not the URs. These results, which are consistent with previous reports, indicate that claustral neurons’ activity is directly involved in cognitive aspects rather than in the kinematics of the CRs of the process of acquiring eyeblink CRs, even using a simple delay paradigm (previously ascribed to other structures). Therefore, the CL could be an important new target in treating cognitive deficits related to attention or learning, such as those reported in several neurodevelopmental disorders.