title: Auditory processing assessment suggests that Wistar audiogenic rat neural networks are prone to entrainment.
abstract: Epilepsy is a neurological disease related to the occurrence of pathological oscillatory activity, but the basic physiological mechanisms of seizure remain to be understood. Our working hypothesis is that specific sensory processing circuits may present abnormally enhanced predisposition for coordinated firing in the dysfunctional brain. Such facilitated entrainment could share a similar mechanistic process as those expediting the propagation of epileptiform activity throughout the brain. To test this hypothesis, we employed the Wistar audiogenic rat (WAR) reflex animal model, which is characterized by having seizures triggered reliably by sound. Sound stimulation was modulated in amplitude to produce an auditory steady-state-evoked response (ASSR; -53.71Hz) that covers bottom-up and top-down processing in a time scale compatible with the dynamics of the epileptic condition. Data from inferior colliculus (IC) c-Fos immunohistochemistry and electrographic recordings were gathered for both the control Wistar group and WARs. Under 85-dB SLP auditory stimulation, compared to controls, the WARs presented higher number of Fos-positive cells (at IC and auditory temporal lobe) and a significant increase in ASSR-normalized energy. Similarly, the 110-dB SLP sound stimulation also statistically increased ASSR-normalized energy during ictal and post-ictal periods. However, at the transition from the physiological to pathological state (pre-ictal period), the WAR ASSR analysis demonstrated a decline in normalized energy and a significant increase in circular variance values compared to that of controls. These results indicate an enhanced coordinated firing state for WARs, except immediately before seizure onset (suggesting pre-ictal neuronal desynchronization with external sensory drive). These results suggest a competing myriad of interferences among different networks that after seizure onset converge to a massive oscillatory circuit.
authors.affiliation: Núcleo de Neurociências (NNC), Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas - Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais CEP 31270-901, Brazil.
authors.forename: Hyorrana Priscila Pereira
authors.initials: HP
authors.lastname: Pinto
authors.affiliation: Núcleo de Neurociências (NNC), Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas - Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais CEP 31270-901, Brazil; Programa de Pós-Graduação em Engenharia Elétrica - Escola de Engenharia - Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais CEP 31270-901, Brazil.
authors.forename: Vinícius Rezende
authors.initials: VR
authors.lastname: Carvalho
authors.affiliation: Núcleo de Neurociências (NNC), Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas - Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais CEP 31270-901, Brazil; Programa de Pós-Graduação em Engenharia Elétrica - Escola de Engenharia - Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais CEP 31270-901, Brazil; Centro de Tecnologia e Pesquisa em Magneto Ressonância - CTPMAG - Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Daniel de Castro
authors.initials: DC
authors.lastname: Medeiros
authors.affiliation: Núcleo de Neurociências (NNC), Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas - Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais CEP 31270-901, Brazil.
authors.forename: Ana Flávia Santos
authors.initials: AF
authors.lastname: Almeida
authors.affiliation: Núcleo de Neurociências (NNC), Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas - Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais CEP 31270-901, Brazil; Programa de Pós-Graduação em Engenharia Elétrica - Escola de Engenharia - Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais CEP 31270-901, Brazil; Centro de Tecnologia e Pesquisa em Magneto Ressonância - CTPMAG - Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Eduardo Mazoni Andrade Marçal
authors.initials: EM
authors.lastname: Mendes
authors.affiliation: Núcleo de Neurociências (NNC), Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas - Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais CEP 31270-901, Brazil; Programa de Pós-Graduação em Engenharia Elétrica - Escola de Engenharia - Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais CEP 31270-901, Brazil; Centro de Tecnologia e Pesquisa em Magneto Ressonância - CTPMAG - Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil. Electronic address: mfdm@ufmg.br.
authors.forename: Márcio Flávio Dutra
authors.initials: MF
authors.lastname: Moraes
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001303:Auditory Cortex / Q000378:metabolism / Q000503:physiopathology*; D003344:Cortical Synchronization; D004195:Disease Models, Animal; D004569:Electroencephalography; D005072:Evoked Potentials, Auditory; D007245:Inferior Colliculi / Q000378:metabolism / Q000503:physiopathology*; D009434:Neural Pathways / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000503:physiopathology*
chemical_list: D016760:Proto-Oncogene Proteins c-fos
keywords: audiogenic seizures; auditory steady state response; desynchronization; hyperexcitability