Regulation of intermittent oscillatory activity of pyramidal cell neurons by GABA inhibitory interneurons is impaired in schizophrenia: rationale for pharmacotherapeutic GABAergic interventions.
GABA, the major inhibitory neurotransmitter in the brain, is synthesized from L-glutamate and packaged within a family of highly differentiated inhibitory interneurons. Individual GABA inhibitory interneurons in the frontal cortex can make terminal synaptic connections with more than 200 distinct pyramidal neurons, the principal output neuron. Moreover, the sites of these synaptic connections include shafts of dendritic spines, soma, dendritic branches, and initial axon segments. The phasic activity of GABAergic neurons regulate intermittent oscillations of assemblies of pyramidal cell neurons, which are critical for many higher cortical functions such as working memory. Potentially, there are several viable pharmacotherapeutic strategies for facilitating GABAergic neurotransmission. A major research question is whether tonically-administered, selective GABAergic therapeutic interventions can mimic and correct disruptions of the intermittent oscillatory activity of assemblies of cortical pyramidal cell neurons.
Deutsch
Stephen I
SI
Department of Psychiatry and Behavioral Sciences, Eastern Virginia Medical School, Norfolk, Virginia 23507-1912, USA. deutscsi@evms.edu
Rosse
Richard B
RB
Schwartz
Barbara L
BL
Mastropaolo
John
J
Burket
Jessica A
JA
Weizman
Abraham
A
D000818:Animals; D001369:Axons / Q000378:metabolism; D001683:Biological Clocks / Q000187:drug effects; D002328:Carisoprodol / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006801:Humans; D007395:Interneurons / Q000378:metabolism*; D008568:Memory; D009433:Neural Inhibition / Q000187:drug effects; D011582:Psychological Theory; D017966:Pyramidal Cells / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018755:GABA Agonists; D018756:GABA Antagonists; D002328:Carisoprodol; D005680:gamma-Aminobutyric Acid