RESUMEN
OBJECTIVES: Neuropeptide Y (NPY) potently suppresses spike-wave discharges (SWDs) in a genetic rat model of absence epilepsy (GAERS), but the underlying neurophysiologic mechanisms are not clear. We therefore sought to determine the in vivo effects of NPY on neuronal firing in the cortico-thalamo-cortical network activity, known to play a critical role in the generation of SWDs in these rats. METHODS: NPY was administered intracerebroventricularly (ICV) or in separate experiments locally on the neurons of caudal thalamic reticular nucleus (NRT) by use of juxtacellular iontophoresis in triple-barrel electrodes in male GAERS aged 12-15 weeks, in vivo under neuroleptic anesthesia. Drug infusions and electroencephalography (EEG) monitoring were performed simultaneously with juxtacellular single neuronal recordings. Effect of NPY on electrically induced SWD induction threshold were also measured. RESULTS: NPY administration ICV led to a decrease in the total length of SWDs in EEG recordings. Both ICV administration and iontophoresis of NPY on NRT neurons led to an increase in interictal neuronal firing of NRT neurons. During ictal periods, ICV NPY administration reduced the number of thalamic action potentials per SWDs, as well as reduced waveform correlations between field potentials within the NRT and the cortical EEG. NPY administration ICV did not significantly alter the firing patterns of relay thalamic neurons interictally and cortical neurons during ictal and interictal periods. In addition, SWD induction threshold in the S2 region of the cortex was significantly increased after NPY administration. SIGNIFICANCE: Our results show alterations in cortico-thalamo-cortical local and network properties following ICV administration of NPY, suggesting mechanisms of SWD suppression in GAERS. Cellular and network alteration of NRT activity, resulting from a direct action of NPY, may be a contributor to this effect.
Asunto(s)
Epilepsia Tipo Ausencia/fisiopatología , Potenciales Evocados/fisiología , Núcleos Talámicos Intralaminares/fisiología , Red Nerviosa/fisiopatología , Neuropéptido Y/fisiología , Núcleos Talámicos/fisiología , Animales , Corteza Cerebral/fisiopatología , Modelos Animales de Enfermedad , Electrodos Implantados , Electroencefalografía , Masculino , Neuronas/fisiología , RatasRESUMEN
Single neuronal juxtacellular recording with simultaneous cortical electroencephalogram (EEG) in whole-animal preparations in vivo has allowed the study of the behaviour of individual neurons in relation to whole brain activity. Data on single neuron firing, neural synchrony, network behaviour and their responses to pharmacological agents can be obtained with dual recordings. However, pharmacological effects on cellular and network activity during paired single-unit recordings have not been possible due to the difficulties in maintaining recordings of two cells for a prolonged period. Here, we describe a method of maintaining stable dual cell juxtacellular recordings from distinct brain regions, allowing the assessment of single unit activity before, during and after the intracerebroventricular (ICV) injection of drugs. Data collection using this technique allows correlation both between the two cells and with whole-brain EEG, and their responses to pharmacological interventions. This is particularly useful for the investigation of the effects of anti-epileptic drugs on animal models of epilepsy, where single unit activity of two cells from distinct regions can be correlated with each other and with whole-brain activity during pre-ictal, ictal and interictal states. We also describe standardised analytical methods of quantifying cell firing patterns, the rhythmicity of individual neurons and the synchronicity of firing between two neurons in ictal and interictal periods and their responses to drug exposure.
Asunto(s)
Anticonvulsivantes/administración & dosificación , Encéfalo/efectos de los fármacos , Electrofisiología/métodos , Vías Nerviosas/efectos de los fármacos , Neuronas/efectos de los fármacos , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Animales , Modelos Animales de Enfermedad , Epilepsia Tipo Ausencia/fisiopatología , Infusiones Intraventriculares , Masculino , RatasRESUMEN
PURPOSE: The origin of bilateral synchronous spike-and-wave discharges (SWDs) that underlie absence seizures has been widely debated. Studies in genetic rodent models suggest that SWDs originate from a restricted region in the somatosensory cortex. The properties of this initiation site remain unknown. Our goal was to characterize the interictal, preictal and ictal neuronal activity in the primary and secondary cortical regions (S1, S2) and in the adjacent insular cortex (IC) in Genetic Absence Epilepsy Rats from Strasbourg (GAERS). METHODS: We performed electroencephalography (EEG) recordings in combination with multisite local field potential (LFP) and single cell juxtacellular recordings, and cortical electrical stimulations, in freely moving rats and those under neurolept-anesthesia. KEY FINDINGS: The onset of the SWDs was preceded by 5-9 Hz field potential oscillations, which were detected earlier in S2 and IC than in S1. Sustained SWDs could be triggered by a 2-s train of 7-Hz electrical stimuli at a lower current intensity in S2 than in S1. In S2 and IC, subsets of neurons displayed rhythmic firing (5-9 Hz) in between seizures. S2 and IC layers V and VI neurons fired during the same time window, whereas in S1 layer VI, neurons fired before layer V neurons. Just before the spike component of each SW complex, short-lasting high-frequency oscillations consistently occurred in IC â¼20 msec before S1. SIGNIFICANCE: Our findings demonstrate that the S2/IC cortical areas are a critical component of the macro-network that is responsible for the generation of absence-related SWDs.