ABSTRACT
Traditional descriptions of the cortical cholinergic input system focused on the diffuse organization of cholinergic projections and the hypothesis that slowly changing levels of extracellular acetylcholine (ACh) mediate different arousal states. The ability of ACh to reach the extrasynaptic space (volume neurotransmission), as opposed to remaining confined to the synaptic cleft (wired neurotransmission), has been considered an integral component of this conceptualization. Recent studies demonstrated that phasic release of ACh, at the scale of seconds, mediates precisely defined cognitive operations. This characteristic of cholinergic neurotransmission is proposed to be of primary importance for understanding cholinergic function and developing treatments for cognitive disorders that result from abnormal cholinergic neurotransmission.
Subject(s)
Acetylcholine/metabolism , Cerebral Cortex/physiology , Models, Neurological , Synaptic Transmission/physiology , Acetylcholinesterase/metabolism , Animals , Humans , Signal Transduction/physiology , Synapses/metabolismABSTRACT
The N-methyl-D-aspartate (NMDA) receptor system is thought to be underactive in schizophrenia which may contribute to attentional dysfunction in this disease. In a visual signal detection task that required discrimination of signaled-trials from trials with no signal, the NMDA receptor antagonist, dizocilpine (0.05 mg/kg), increased errors on non-signal trials. Co-administration of dizocilpine and 10.0 mg/kg D-cycloserine, a co-agonist at the glycine site on the NMDA receptor, significantly decreased the error rate on non-signal trials compared to dizocilpine alone. These results suggest that drugs targeting the glycine site may be beneficial for attenuating attentional deficits associated with an underactive NMDA receptor system.
