GABA A receptor mediated inhibition contributes to corticostriatal frequency filtering

摘要

The striatum plays an important role in the initiation and learning of skilled motor behavior [6] and receives topographic input from most areas of the cortex. Cortical afferents make divergent contact with many striatal medium spiny neurons while individual medium spiny neurons receive tens of thousands of these glutamatergic synapses [13]. Temporal filtering of frequency information within synaptic fields plays an important role in the processing of neuronal signals. We have previously shown differential filtering characteristics within CA1, CA3, and the dentate gyrus of the hippocampus [26] and have now extended these studies to the cortical input to the dorsal striatum in order to address the network filtering characteristics in this important synaptic field. We measured field potentials of striatal medium spiny neurons in response to layer V cortical input over a range of stimulus frequencies from 2Hz to 100Hz. The average population spike amplitude in response to these stimulus trains exhibited a non-linear relationship to frequency, with characteristics of a low pass filter. In order to assess potential modulation of these filter properties, we examined the frequency response in the presence of antagonists to CB1, D2, nACh, and GABA A receptors, which are all known to be expressed at these synapses [13]. Of these, only GABA A receptor antagonists significantly modulated the frequency filtering characteristics over the examined frequency range. High frequency stimulation induces long term plasticity at corticostriatal synapses [4] and this process is strengthened when GABA A receptors are blocked [7,20,29]. Our results suggest a model whereby a temporary decrease in GABA level would modulate the filtering parameters of the corticostriatal circuit, allowing a more robust induction of high frequency-dependent plasticity.