Biomaterial Database

Dopaminergic modulation of the P50 auditory-evoked potential in a computer model of the CA3 region of the hippocampus: its relationship to sensory gating in schizophrenia. 2003

Karen A Moxon, and Greg A Gerhardt, and Lawrence E Adler

Drexel University, School of Biomedical Engineering, Science and Health Systems, 3141 Chestnut St., Philadelphia, PA 19104-2875, USA. karen.moxon@drexel.edu

We modeled the neuronal circuits that may underlie a sensory-processing deficit associated with schizophrenia. Schizophrenic patients have small P50 auditory-evoked responses to click stimuli compared to normal subjects. The P50 auditory-evoked response is a positive waveform recorded in the EEG approximately 50 ms after the auditory click stimulus. In addition to relatively small amplitudes, schizophrenic patients do not gate or suppress the P50 auditory-evoked response to the second of two paired-click stimuli spaced 0.5 s apart. Neuropleptic medication, which decreases dopaminergic neuronal transmission, increases the amplitude of the P50 auditory-evoked response but does not improve gating. Normal subjects have large P50 auditory-evoked responses to click stimuli when compared to unmedicated schizophrenic patients, and they gate their response to paired click stimuli or have smaller P50 auditory-evoked response amplitudes to the second of two click stimuli spaced 0.5 s apart. Schizophrenic patients do not gate and have similar response amplitudes to both clicks. We hypothesized that the small amplitudes of unmedicated schizophrenic subjects were due to a state of occlusion whereby excessive background noise in local circuits reduced the ability of cells to respond synchronously to sensory input, thereby reducing the amplitude of the P50 waveform in the EEG. Because the P50 auditory-evoked potential amplitudes increased with neuroleptic medication, which reduces dopaminergic neuronal transmission, we hypothesized a role for dopamine in modulating the signal-to-noise (S/N) in the local circuits responsible for sensory gating. To test the hypothesis that modulation of the S/N ratio reduces sensory gating, we developed a model of the effects of dopaminergic neuronal transmission that modulates the S/N in neuronal circuits. The model uses the biologically relevant computer model of the CA3 region of the hippocampus developed in the companion paper [Moxon et al. (2003) Biol Cybern, this volume]. Modified Hebb cell assemblies represented the response of the network to the click stimulus. The results of our model showed that excessive dopaminergic input impaired the ability of cells to respond synchronously to sensory input, which reduced the amplitudes of the P50 evoked responses.

UI	MeSH Term	Description	Entries
D008959	Models, Neurological	Theoretical representations that simulate the behavior or activity of the neurological system, processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.	Neurologic Models,Model, Neurological,Neurologic Model,Neurological Model,Neurological Models,Model, Neurologic,Models, Neurologic
D009433	Neural Inhibition	The function of opposing or restraining the excitation of neurons or their target excitable cells.	Inhibition, Neural
D009435	Synaptic Transmission	The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.	Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D011930	Reaction Time	The time from the onset of a stimulus until a response is observed.	Response Latency,Response Speed,Response Time,Latency, Response,Reaction Times,Response Latencies,Response Times,Speed, Response,Speeds, Response
D011978	Receptors, Nicotinic	One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.	Nicotinic Acetylcholine Receptors,Nicotinic Receptors,Nicotinic Acetylcholine Receptor,Nicotinic Receptor,Acetylcholine Receptor, Nicotinic,Acetylcholine Receptors, Nicotinic,Receptor, Nicotinic,Receptor, Nicotinic Acetylcholine,Receptors, Nicotinic Acetylcholine
D003198	Computer Simulation	Computer-based representation of physical systems and phenomena such as chemical processes.	Computational Modeling,Computational Modelling,Computer Models,In silico Modeling,In silico Models,In silico Simulation,Models, Computer,Computerized Models,Computer Model,Computer Simulations,Computerized Model,In silico Model,Model, Computer,Model, Computerized,Model, In silico,Modeling, Computational,Modeling, In silico,Modelling, Computational,Simulation, Computer,Simulation, In silico,Simulations, Computer
D004298	Dopamine	One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.	Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D005072	Evoked Potentials, Auditory	The electric response evoked in the CEREBRAL CORTEX by ACOUSTIC STIMULATION or stimulation of the AUDITORY PATHWAYS.	Auditory Evoked Potentials,Auditory Evoked Response,Auditory Evoked Potential,Auditory Evoked Responses,Evoked Potential, Auditory,Evoked Response, Auditory,Evoked Responses, Auditory,Potentials, Auditory Evoked
D006624	Hippocampus	A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.	Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums