Störungen der glutamatergen Aktivierung limbisch-kortikaler Interneurone — ein zelluläres Psychosemodell?

Grunze, Heinz; Kammerer, C.

doi:10.1007/978-3-7091-6471-6_9

Cited by 1 publication

(1 citation statement)

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“…High synchronicity of the cortical glutamatergic input is more likely to overcome the dopaminergic inhibition, leading downstream from the mesolimbic projection neuron finally to an improvement in the thalamic filter function. 18 Some neuroleptics may exert a dual action in balancing the relationship between dopaminergic and glutamatergic input, eg, haloperidol, which also has glutamatergic agonist properties byenhancing NMDA receptor sensitivity. 19 - 21 …”

Section: Resultsmentioning

confidence: 99%

Neurotoxicity of NMDA antagonists: a glutamatergic theory of schizophrenia based on selective impairment of local inhibitory feedback circuits

Grunze

Bender

Wendhof³

et al. 2000

Dialogues in Clinical Neuroscience

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Modulation of recurrent inhibition is critical not only for the normal function of highly excitable regions of the brain, especially the limbic system, but may also be a primary determining factor for the viability of neurons in these regions. Standard extracellular and intracellular recordings from in vitro brain slices of rat hippocampi were employed to show that recurrent inhibition onto CA1 neurons can be modulated by N-methyl-D-aspartate (NMDA) antagonists. Besides reducing the amplitude of inhibitory postsynaptic potentials (IPSPs) at resting membrane potential conditions, different NMDA antagonists, including the endogenous substance N-acetyl-L-aspartyl-L-glutamic acid (NAAG), are able to block long-term potentiation (LIP) of recurrent inhibition completely at concentrations that are not sufficient to block LTP of the excitatory drive onto pyramidal neurons. This LTP of recurrent inhibition may play a significant role in stimulus discrimination and learning, as simulated in a biophysical computer model of a basic neuronal circuit. Both the amplitude of the IPSP and LTP of the recurrent inhibitory circuit also undergo developmental changes showing their highest expression and vulnerability to chronic NMDA antagonist injections in juvenile rats. Finally, blocking NMDA receptor-dependent transmission in the recurrent inhibition loop may lead to an overall increased excitability of the neuronal network. This may resemble the positive schizophrenic symptoms observed in man, presumably caused by elevated levels of the endogenous NMDA antagonist NAAG.

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Section: Resultsmentioning

confidence: 99%