RESUMO
Spike-timing modifies the efficacy of both excitatory and inhibitory synapses onto CA1 pyramidal neurons in the rodent hippocampus. Repetitively spiking the presynaptic neuron before the postsynaptic neuron induces inhibitory synaptic plasticity, which results in a depolarization of the reversal potential for GABA (E(GABA)). Our goal was to determine how inhibitory synaptic plasticity regulates CA1 pyramidal neuron spiking in the rat hippocampus. We demonstrate electrophysiologically that depolarizing E(GABA) by 24.7 mV increased the spontaneous action potential firing frequency of cultured hippocampal neurons 254% from 0.12+/-0.07 Hz to 0.44+/-0.13 Hz (n=11; P<0.05). Next we used a single compartment model of a CA1 pyramidal neuron to explore in detail how inhibitory synaptic plasticity of feedforward and feedback inhibition regulates the generation of action potentials, spike latency, and the minimum excitatory conductance required to generate an action potential; plasticity was modeled as a depolarization of E(GABA), which effectively weakens inhibition. Depolarization of E(GABA) at feedforward and feedback inhibitory synapses decreased the latency to the 1st spike by 2.27 ms, which was greater that the sum of the decreases produced by depolarizing E(GABA) at feedforward (0.85 ms) or feedback inhibitory synapses (0.02 ms) alone. In response to a train of synaptic inputs, depolarizing E(GABA) decreased the inter-spike interval and increased the number of output spikes in a frequency dependent manner, improving the reliability of input-output transmission. Moreover, a depolarizing shift in E(GABA) at feedforward and feedback synapses triggered by spike trains recorded from CA1 pyramidal layer neurons during field theta from anesthetized rats, significantly increased spiking on the up- and down-strokes of the first half of the theta rhythm (P<0.05), without changing the preferred phase of firing (P=0.783). This study provides the first explanation of how depolarizing E(GABA) affects pyramidal cell output within the hippocampus.
Assuntos
Potenciais de Ação/fisiologia , Hipocampo/citologia , Inibição Neural/fisiologia , Plasticidade Neuronal/fisiologia , Células Piramidais/fisiologia , Sinapses/fisiologia , Potenciais de Ação/efeitos da radiação , Análise de Variância , Animais , Células Cultivadas , Estimulação Elétrica , Embrião de Mamíferos , Feminino , Modelos Neurológicos , Dinâmica não Linear , Técnicas de Patch-Clamp/métodos , Gravidez , Células Piramidais/efeitos da radiação , Ratos , Ratos Sprague-Dawley , Tempo de Reação , Sinapses/efeitos da radiação , Transmissão SinápticaRESUMO
It is well known that interneurons are heterogeneous in their morphologies, biophysical properties, pharmacological sensitivities and electrophysiological responses, but it is unknown how best to understand this diversity. Given their critical roles in shaping brain output, it is important to try to understand the functionality of their computational characteristics. To do this, we focus on specific interneuron subtypes. In particular, it has recently been shown that long-term potentiation is induced specifically on oriens-lacunosum/moleculare (O-LM) interneurons in hippocampus CA1 and that the same cells contain the highest density of dendritic sodium and potassium conductances measured to date. We have created multi-compartment models of an O-LM hippocampal interneuron using passive properties, channel kinetics, densities and distributions specific to this cell type, and explored its signalling characteristics. We found that spike initiation depends on both location and amount of input, as well as the intrinsic properties of the interneuron. Distal synaptic input always produces strong back-propagating spikes whereas proximal input could produce both forward- and back-propagating spikes depending on the input strength. We speculate that the highly active dendrites of these interneurons endow them with a specialized function within the hippocampal circuitry by allowing them to regulate direct and indirect signalling pathways within the hippocampus.
Assuntos
Dendritos/fisiologia , Hipocampo/fisiologia , Interneurônios/fisiologia , Modelos Neurológicos , Potenciais de Ação/fisiologia , Animais , Axônios/fisiologia , Eletrofisiologia , Hipocampo/citologia , Camundongos , Camundongos Endogâmicos C57BL , Condução Nervosa/fisiologia , Tempo de Reação , Sinapses/fisiologiaRESUMO
Recent experimental and model work indicates that slowly inactivating potassium currents might play critical roles in generating population rhythms. In particular, slow (<1-4 Hz) rhythms recorded in the hippocampus correlate with oscillatory behaviors in interneurons in this frequency range. Limiting the ion channels to the traditional Hodgkin-Huxley sodium and potassium currents, a persistent sodium current, and a slowly inactivating potassium current, we explore the role of slowly inactivating conductances in a multi-compartmental interneuronal model. We find a rich repertoire of tonic and bursting behaviors depending on the distribution, density and kinetics of this conductance. Specifically, burst frequencies of appropriate frequencies could be obtained for certain distributions and kinetics of this conductance. Robust (with respect to injected currents) regimes of tonic firing and bursting behaviors are uncovered. In addition, we find a bistable tonic firing pattern that depends on the slowly inactivating potassium current. Therefore, this work shows ways in which different channel distributions and heterogeneities could produce variable signal outputs. We suggest that an understanding of the dynamical profiles of inhibitory neurons based on the density and distribution of their currents is helpful in dissecting out the complex roles played by this heterogeneous group of cells.