Journal of Neuroscience, Vol 8, 3750-3756, Copyright © 1988 by Society for Neuroscience
Presynaptic actions of carbachol and adenosine on corticostriatal synaptic transmission studied in vitro
RC Malenka and JD Kocsis
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, California 94305.
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)