Society of biological psychiatry 2001 annual meeting
Long-lasting, activity-dependent changes in synaptic strength at excitatory synapses in the mammalian brain are thought to play critical roles in brain development and many forms of experiencedependent behavioral plasticity. The most well-understood forms of synaptic plasticity are NMDA receptor-dependent long-term potentiation (LTP) and long-term depression (LTD) which have been studied most extensively in the hippocampus. Methods: In addition to discussing the molecular mechanisms underlying
... TP and LTD, examples of their potential functional roles in vivo in experience-dependent plasticity will also be presented. Results: LTP and LTD are triggered by different patterns of synaptic activity which lead to the calcium-dependent activation of postsynaptic protein kinases or protein phosphatases, respectively. Activation of these intracellular signaling cascades in turn appear to bi-directionally control synaptic strength, at least in part, by regulation of the trafficking of glutamate receptors to (LTP) and away from (LTD) synapses. Abstract not available. Background: Drug addiction may characterized as a disorder of neural plasticity, in which inappropriate recruitment of associative learning mechanisms leads to compulsive drug use and long-term risk of cuedependent relapse. Addictive drugs promote dopamine release in multiple forebrain regions. In the dorsal and ventral striatum, dopamine can act as a reinforcement signal controlling learning processes. At the molecular level, stimulation of dopamine D1 receptors in the striatum promotes activation of the transcription factor CREB. CREB-dependent signaling events have been implicated in both invertebrate and vertebrate models of synaptic plasticity and long-term memory. We therefore sought to identify dopamine-inducible striatal genes that are likely CREB targets. Methods: We screened for dopamine-regulated genes and tested their inducibility by psychostimulant and antipsychotic drugs. Genes that were likely candidates for involvement in dopamine-induced synaptic plasticity were chosen for further analysis. Results: 35 dopamine-inducible genes were identified in striatum. Genes were induced in D1 expressing neurons in response to cocaine and in D2 receptor-containing neurons in response to eticlopride. All examined in detail appeared to have characteristics of immediate early genes (IEGs). The IEGs identified appear to have diverse functions based on the predicted proteins and on subcellular localization. Several genes, including a novel dopamine-inducible cyclin were further studied. Aspects of regulation and possible function will be described. Conclusions: The ability of addictive drugs to facilitate long-term associative memory formation may result from the ability of dopamine to elicit a complex but transient program of gene expression that leads to lasting synaptic changes.