Chronic Intermittent Hypoxia Depresses Afferent Neurotransmission in NTS Neurons by a Reduction in the Number of Active Synapses

Autor(es)

Almado, Carlos Eduardo L. ^[1] ; Machado, Benedito H. ^[1] ; Leao, Ricardo M. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Physiol, BR-14049900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF NEUROSCIENCE; v. 32, n. 47, p. 16736-16746, NOV 21 2012.
• Citações Web of Science: 30

Resumo

Long-term synaptic plasticity has been recently described in brainstem areas associated to visceral afferent sensory integration. Chronic intermittent hypoxia (CIH), an animal model for studying obstructive sleep apnea in humans, depresses the afferent neurotransmission in nucleus tractus solitarii (NTS) neurons, which affect respiratory and autonomic regulation. Here we identified the synaptic mechanisms of CIH-induced depression of the afferent neurotransmission in NTS neurons in juvenile rats. We verified that CIH reduced the amplitude of both NMDA and non-NMDA glutamatergic excitatory currents (eEPSCs) evoked by tractus solitarii stimulation (TS-eEPSC) of second-order neurons in the NTS. No changes were observed in release probability, evidenced by absence of any CIH-elicited effects on short-term depression and failures in EPSCs evoked in low calcium. CIH also produced no changes in TS-eEPSC quantal size, since the amplitudes of both low calcium-evoked EPSCs and asynchronous TS-eEPSCs (evoked in the presence of Sr2+) were unchanged. Using single TS afferent fiber stimulation in slices from control and CIH rats we clearly show that CIH reduced the quantal content of the TS-eEPSCs without affecting the quantal size or release probability, suggesting a reduction in the number of active synapses as the mechanism of CIH induced TS-eEPSC depression. In accordance with this concept, the input-output relationship of stimulus intensity and TS-eEPSC amplitude shows an early saturation in CIH animals. These findings open new perspectives for a better understanding of the mechanisms underlying the synaptic plasticity in the brainstem sensory neurons under challenges such as those produced by CIH in experimental and pathological conditions. (AU)

• Processo FAPESP: 08/04618-0 - Caracterização eletrofisiológica, sináptica e molecular dos neurônios Nidopálio Caudomedial uma área responsável pelo processamento auditivo em aves canoras.
• Beneficiário: Ricardo Mauricio Xavier Leão
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 08/54953-0 - Caracterização eletrofisiológica dos neurônios do núcleo do trato solitário e do bulbo ventrolateral de ratos jovens
• Beneficiário: Carlos Eduardo Lopes Almado
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto