Wyniki wyszukiwania - Biblioteka Nauki

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Ekonomiczne aspekty zagospodarowania i ochrony terenow podmoklych doliny Biebrzy i Narwi

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Dobrzanski G.

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nr 1

105-114

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The dreadd agonist, CNO, does not affect learning-dependent cortical plasticity

51%

Dobrzanski G. , Zakrzewska R. , Kossut M.

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nr Suppl.1

EN

INTRODUCTION: Associative fear learning, in which stimulation of vibrissae is paired with tail shock results in increased functional cortical representation of the row of whiskers activated during the conditioning. Expansion of the functional cortical representation was revealed with 2-deoxyglucose autoradiography. The chemogenetic DREADD technique allows for precise manipulation of the brain circuits and is based on exclusive activation of designer receptors by designer drug – CNO (Clozapine N-oxide). CNO, which is believed to be pharmacologically inert in mice and rats but not in humans, recently was found to produce some behavioural effects in one of the rat’s strain. AIM(S): Taking into account the possible unspecific results in our chemogenetic experiments in mice, we aimed to determine if CNO administered alone can influence the learning-dependent plasticity. METHOD(S): A group of wild type, C57BL/6J mice underwent behavioural training consisting of 3 sessions of conditioning in three consecutive days. 30 minutes before each session mice were injected intraperitoneally with CNO (1 mg/kg). 24 hours after the third session 2-deoxyglucose procedure was performed. Autoradiograms of tangential brain sections containing the barrel field were analyzed and functional representation of the conditioned row of whiskers and contralateral row on the other side of the snout were mapped. RESULTS: Analysis showed the increased representation of the trained row in the fourth layer of barrel cortex in conditioned hemisphere in comparison to control one. Cortical activity was also observed in other structures like secondary somatosensory cortex and auditory cortex, which replicate the pattern of activation observed in previous experiments. CONCLUSIONS: The results suggest that CNO administered alone does not influence the learning‑‑dependent cortical plasticity and can be applied in chemogenetic experiments within this experimental model of learning in mice. FINANCIAL SUPPORT: Authors are supported by the Polish National Science Centre Grant given to Małgorzata Kossut (2015/17/B/NZ4/02016).

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Chemogenetic inhibition of somatostain interneurons alters plasticity induced by sensory deprivation in the barrel cortex of mice

51%

Dobrzanski G. , Lukomska A. , Zakrzewska R. , Kossut M.

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nr Suppl.1

EN

INTRODUCTION: Among cortical inhibitory cells, activity of somatostatin interneurons (SST INTs) has been recently proposed as a key player in the formation of neuroplastic changes. Sensory deprivation causes changes in inhibitory systems that lead to disinhibition of the spared barrel, allowing for spreading of its functional representation. Because of their unique pattern of connectivity, we hypothesize that layer IV SST INTs strongly modulate disinhibition of the spared barrel, supporting the sensory deprivation‑induced plastic change formation. AIM(S): Using a chemogenetic approach, we aimed to study a direct role of layer IV SST INTs activity in plastic change formation induced by sensory deprivation in mice barrel cortex. METHOD(S): SST-Cre mice were unilaterally injected with Cre-dependent AAV2 vectors expressing inhibitory DREADDs into a single barrel of row C. Two weeks later, mice underwent a sensory deprivation paradigm, in which all whiskers but one, C3, on one side of the snout were plucked for a week. During deprivation, the activity of SST INTs was blocked by DREADDs activation with its agonist, CNO, continuously administered via Alzet® Osmotic Pumps. To visualize plastic change, [14C]‑2‑deoxyglucose brain mapping was performed. The area of functional representation of the spared whisker and contralateral one was compared. RESULTS: We found that SST INTs inhibition in the spared barrel did not influence the area of activation of the spared whisker compared to transduced animals with saline administration instead of CNO. However, SST INTs blockade in the deprived barrel, adjacent to the spared one, led to a dramatic decrease in functional plasticity of spared whisker representation. CONCLUSIONS: Our results indicate that layer IV SST INTs activity in deprived, but not spared barrel, is essential in sensory deprivation-induced plastic change formation in the barrel cortex of mice. FINANCIAL SUPPORT: Polish National Science Centre Grant to GD (2017/27/N/NZ4/02639).