Presynaptic actions of carbachol and adenosine on corticostriatal synaptic transmission studied in vitro

Abstract

The purpose of this study was to identify, in the in vitro rat neostriatal slice preparation, an electrophysiological response corresponding to the activation of striatal neurons by cortical afferents, and to study the actions of a variety of putative neurotransmitters on modulating synaptic transmission at this synapse. Local stimulation of the neostriatal slice evokes a field potential composed of 2 prominent negativities. Experiments using calcium antagonists and tetrodotoxin indicate that the first negativity (N1) reflects the direct activation of intrinsic neurons and axons, while the second negativity (N2) is synaptically mediated. The afferent fibers eliciting the second negativity have not previously been identified because of the mixing of afferents within the striatum. However, similar field potential responses are elicited by stimulation of the corpus callosum, in which the only striatal afferents are crossed corticostriatal fibers. Kynurenate, gamma-D-glutamylglycine, and piperidine dicarboxylate all reversibly reduced or abolished N2, suggesting that the transmitter generating the response is an excitatory amino acid. Together, these results strongly suggest that N2 reflects activation of striatal neurons by corticostriatal afferents. Three putative striatal neurotransmitters, dopamine, acetylcholine and adenosine, were studied with respect to their ability to modulate the corticostriatal response. Dopamine had minimal effects on the waveform of the field potential. In contrast, carbachol or adenosine consistently reversibly reduced or eliminated N2. Atropine blocked carbachol's actions, while theophylline blocked adenosine's actions, indicating that the compounds were acting on muscarinic and adenosine receptors, respectively. To test whether these were primarily pre- or postsynaptic actions, we recorded the response to ionophoretically applied glutamate while simultaneously recording the synaptically evoked field potential from the same location.(ABSTRACT TRUNCATED AT 250 WORDS)