Study of the salycilate effects on the neurotransmission and excitability of the neurons from the Dorsal Cochlear Nucleus (DCN)

• Grant number: 12/09421-6
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2012
• End date: August 31, 2015
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Ricardo Mauricio Xavier Leão
• Grantee: Ricardo Mauricio Xavier Leão
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Salicylate intoxication leads to the development of tinnitus in humans and experimental animals. Hyperactivity in the Dorsal Cochlear Nucleus (DCN) is related to the development of tinnitus, and acute applications of salicylate increase the firing of fusiform (principal) neurons of DCN in vivo. However, both the mechanisms of hyperactivity in the DCN after tinnitus and salicylate poisoning are unknown. In this project we will test the hypothesis that salicylate changes the excitability of DCN altering the balance of excitation and inhibition in this nucleus. The DCN has a feed-forward inhibitory circuit which combines an excitatory current with a inhibitory current from a interneuron. Cartwheel Neurons are the main source of inhibition of principal neurons of the DCN, and receive synapses from granule neurons, which mediate the transmission of somatosensory information that reaches the DCN. Salicylate is an inhibitor of leukotriene and prostglandinas synthesis by ciclooxygenases. Endocannabinoids mediate long-term depression of excitatory neurotransmission in neurons cartwheel and can be degraded by ciclooxygenases. Excess of endocannabinoids after salycilate could affect the balance of excitation and inhibition in the DCN by affecting the neurotransmission on cartwheel neurons To better understand the actions of salicylate on the balance excitation / inhibition in DCN propose to study the effects of applying salicylate in vitro on the neurotransmission and plasticity mediated by endocannabinoids in cartwheel and fusiform neurons in the DCN. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CUNHA, A. O. S.; DE OLIVEIRA, J. A. C.; ALMEIDA, S. S.; GARCIA-CAIRASCO, N.; LEAO, R. M.. INHIBITION OF LONG-TERM POTENTIATION IN THE SCHAFFER-CA1 PATHWAY BY REPETITIVE HIGH-INTENSITY SOUND STIMULATION. Neuroscience, v. 310, p. 114-127, DEC 3 2015. (12/09421-6)

DAGOSTIN, ANDRE A.; LOVELL, PETER V.; HILSCHER, MARKUS M.; MELLO, CLAUDIO V.; LEAO, RICARDO M.. Control of Phasic Firing by a Background Leak Current in Avian Forebrain Auditory Neurons. FRONTIERS IN CELLULAR NEUROSCIENCE, v. 9, DEC 10 2015. (08/04618-0, 12/09421-6, 08/10015-7)

ZUGAIB, JOAO; CEBALLOS, CESAR C.; LEAO, RICARDO M.. High doses of salicylate reduces glycinergic inhibition in the dorsal cochlear nucleus of the rat. HEARING RESEARCH, v. 332, p. 188-198, FEB 2016. (12/09421-6)