Frontal Lobe Synaptic Plasticity in Development and Disease: Modulation by the Dopamine D1 Receptor

Author(s): Lynn D. Selemon.

Journal Name: Current Pharmaceutical Design

Volume 20 , Issue 32 , 2014


Synaptic plasticity is now known to occur at glutamate synapses throughout the brain, including the neocortex, and to play a role in neurodevelopment as well as in a broad spectrum of adult neural functions. Here the hypothesis that synaptic plasticity, specifically long term depression, is the neural substrate that mediates adolescent synaptic pruning is re-examined in the context of its ramifications for neuropsychiatric illnesses. Stress, which in part is mediated by dopamine acting via the D1 receptor, may disrupt normal synaptic plasticity in adolescence resulting in excessive synaptic elimination. In this manner elevated dopamine levels due to stress could contribute to deficits in gray matter volume and reduced neural connectivity in diseases such as major depressive disorder and schizophrenia. Attention deficit hyperactivity disorder, another developmental illness associated with cortical gray matter volume deficits, may represent a state of diminished dopamine stimulation that is equally disruptive to normal mechanisms of synaptic plasticity. In post-traumatic stress disorder, long term potentiation necessary for conditioned fear extinction, is thought to be impaired. Recent evidence suggests that genotypes related to dopamine neurotransmission confer vulnerability to post-traumatic stress disorder, perhaps indicating that low dopamine levels are less permissive of the synaptic plasticity that underlies consolidation and retention of fear extinction. Further understanding of the role that dopamine-modulated synaptic plasticity plays in development and, when disrupted, in precipitating neuropsychiatric illness could lead to novel drug treatments, and ultimately to preventative pharmacotherapeutic interventions, for these disorders.

Keywords: Long term depression, long term potentiation, glutamate receptors, depression, schizophrenia, attention deficit hyperactivity disorder, post-traumatic stress disorder.

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Article Details

Year: 2014
Page: [5194 - 5201]
Pages: 8
DOI: 10.2174/1381612819666140110122307
Price: $65

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