Muscarinic Cholinergic Inhibition of Glutamatergic Transmission

  • Stephen H. Williams
  • Daniel Johnston


The earliest studies of the actions of acetylcholine (ACh) in the brain indicated that cholinergic agonists had an excitatory effect. Local applications of ACh to the cerebral cortex increased the amplitude of electroencephalogram responses (Sjostrand, 1937) and could induce bursts of spikes (Chatfield and Dempsey, 1941), while intracisternal injections of ACh elicited seizures (Brenner and Merritt, 1942). A systematic study of neurons in the cerebral cortex demonstrated that ionophoretically applied ACh could excite discharges in about 15% of cells tested (Krnjevic and Phillis, 1962; Krnjevic and Phillis, 1963a). The responses had a long latency, modest amplitude, long duration, and a pharmacological profile consistent with activation of muscarinic receptors (Krnjevic and Phillis, 1963b). Later intracellular recordings demonstrated this excitatory effect to be associated with a depolarization and a decrease in potassium conductance (Bernardo and Prince, 1982; Halliwell and Adams, 1982). These excitatory actions are in stark contrast to the depressant effects of muscarinic agonists observed on evoked synaptic activity. These effects were noted in some of the earliest experiments using the brain slice preparation (Yamamoto and Kawai, 1967), and it was speculated that the locus of action for ACh might be the presynaptic terminal. This proposition has been hard to demonstrate directly because of the inaccessibility of the synaptic terminal to experimental manipulations; consequently, the effects of ACh on postsynaptic membrane currents have been more fully analyzed.


Synaptic Transmission Muscarinic Receptor Mossy Fiber Synaptic Current Glutamatergic Transmission 
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© Birkhäuser Boston 1993

Authors and Affiliations

  • Stephen H. Williams
  • Daniel Johnston

There are no affiliations available

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