[The influence of neuromodulators on the synaptic plasticity in dopaminergic structures of the midbrain (hypothetical mechanism)].
A mechanism underlying the effects of neuromodulators on long-term changes in the efficacy of excitatory and inhibitory inputs to dopaminergic and inhibitory cells of the substantia nigra and ventral tegmental area is suggested. According to this mechanism, activation of Gi/0 protein-coupled dopamine D2 autoreceptors and opioid kappa (mu) receptors on dopaminergic (inhibitory) cells promotes the LTD of excitatory inputs to these cells and decrease in their activity. Activation of Gq/11 protein-coupled alpha1 adrenoreceptors, muscarinic M1, neurokinin NK3 (alpha1, M3, NK1, serotonin 5-HT2) receptors on dopaminergic (inhibitory) cells as well as activation of Gs protein-coupled D1 receptors on inhibitory cells promotes the LTP of excitatory inputs to these cells and increase in their activity. Augmenting (lowering) GABA release can be provided by activation of presynaptic D1 and M3 receptors (mu, 5-HT1, and adenosine A1) receptors. Increase (decrease) in GABA concentration due to modulation of inhibitory cell activity and/or GABA release will promote the induction of LTD (LTP) of excitatory inputs to target dopamine cells. The model agree with known experimental data describing the involvement of neuromodulators in modification of dopamine cell activity and dopamine release. The suggested model can be useful in understanding the operation of neuronal networks, which include the basal ganglia.
Sil'kis
I G
IG
Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow.
D017660:Autoreceptors / Q000502:physiology; D001479:Basal Ganglia / Q000502:physiology; D006801:Humans; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008636:Mesencephalon / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology; D011954:Receptors, Dopamine / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
D017660:Autoreceptors; D018377:Neurotransmitter Agents; D011954:Receptors, Dopamine