Instytut Biologii Doświadczalnej im. Marcelego Nenckiego PAN
Urban-Ciećko, Joanna : Supervisor
Instytut Biologii Doświadczalnej im. Marcelego Nenckiego PAN
202 pages : illustrations ; 30 cm ; Bibliography ; Summary in English
Instytut Biologii Doświadczalnej im. Marcelego Nenckiego PAN
The cortical neural network consists of excitatory glutamatergic cells and inhibitory GABAergic interneurons. GABAergic cells regulate the flow of information in local neural networks, affecting the excitability of glutamatergic cells, being responsible for filtering the input signal and controlling the information output. In terms of expression of molecular markers, GABAergic neurons form three classes of cells: somatostatin (Int-SOM), parvalbumin (Int-PV) interneurons, and those expressing the 5HT3a ionotropic serotonin receptor. The last class is divided into interneurons containing vasoactive intestinal polypeptide (Int VIP) and cells not containing this protein. Many studies indicate a wide role of various classes of GABAergic interneurons in processes related to learning, memory formation, as well as its coding and expression. However, less attention has been paid to plastic changes induced by learning within different classes of interneurons. The research included in this dissertation was intended to reveal whether a simple form of learning in mice leads to plastic changes in the electrophysiological activity of three types of GABAergic cells in the layer IV of the primary somatosensory (barrel) cortex: Int SOM, Int-PV, and Int-VIP. For this purpose, one group of animals was subjected to a conditioning procedure consisting of the simultaneous application of a conditioned stimulus, tactile stimulation of the row of whiskers, and an unconditioned electric shock to the tail. A second group of mice underwent a pseudoconditioning procedure in which the electrical stimulus was not time-bound to vibrissae stimulation, but delivered randomly. The last group, naïve animals, has not been subjected to any form of manipulation. One day after the last session of procedures, electrophysiological recordings were carried out from single neurons (whole-cell patch-clamp) in brain slices in layer IV of sensory representations (barrels) corresponding to the stimulated rows of vibrissae. Experiments showed an increase in intrinsic excitability of Int-SOM in conditioned animals compared to pseudoconditioned and naïve animals. In contrast, the excitability of Int PV was reduced in pseudoconditioned mice compared to other groups of mice. Excitability of Int VIP, which were characterized by accommodation of discharges, was found to be reduced in pseudoconditioned mice compared to conditioned but not naïve mice. Analyzes of the action potentials’ shapes mainly showed that the increase in the excitability of interneurons is associated with the shortening of the duration of individual action potentials (reduced half width of the potential). On the other hand, a decrease in excitability meant an increase in the duration of the potentials. The obtained results suggest that the observed changes in the excitability of interneurons may be associated with changes in ionic conductivity responsible for the duration of the action potential. Subsequent studies using optogenetic methods showed that conditioning (but not pseudoconditioning) results in enhanced inhibition of adjacent excitatory neurons by Int SOM and Int-PV, but not Int-VIP. These results indicate that changes in the intrinsic excitability of interneurons and changes in synaptic inhibition coming from these interneurons may be divergent. In conclusion, the obtained results show that both associative learning and pseudoconditioning lead to plastic changes in the activity of all classes of GABAergic interneurons studied. In this way, changes in intrinsic excitability can be seen as a common mechanism of plasticity of GABAergic interneurons occurring as a result of various forms of learning - conditioning or pseudoconditioning. The observed modifications of intrinsic excitability may affect synaptic summation, processing of sensory information, control of the precision of excitatory cell discharges, and regulation of the output of signals transmitted to the higher layers of the barrel cortex.
Nencki Institute of Experimental Biology of the Polish Academy of Sciences
Library of the Nencki Institute of Experimental Biology PAS
Dec 15, 2023
Dec 15, 2023
83
https://rcin.org.pl./publication/276394