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BIO254:Silent: Difference between revisions
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Although LTP was discovered more than three decades ago, the molecular mechanisms contributing to this phenomenon are still not well understood. The properties of NMDA-type glutamate receptors were first elucidated in the mid-1980s, and at about the same time, neurobiologists found that antagonists (inhibitors) of NMDA receptors actually prevented LTP. The "AND" characteristics of NMDA receptors contribute to both the specificity and associativity of LTP. For example, when only one group of synaptic inputs is strongly stimulated, LTP is confined to the active synapses (selectivity), since glutamate opens NMDA receptors only at the stimulated sites. However, in terms of associativity, applying a weakly stimulating input current releases glutamate but cannot depolarize the post-synaptic terminal enough to relieve the Mg++ block. When neighboring stimulations are applied to a weak input, these currents work "associatively" to both depolarize and unblock the NMDA receptors on the cell dendrite. | Although LTP was discovered more than three decades ago, the molecular mechanisms contributing to this phenomenon are still not well understood. The properties of NMDA-type glutamate receptors were first elucidated in the mid-1980s, and at about the same time, neurobiologists found that antagonists (inhibitors) of NMDA receptors actually prevented LTP. The "AND" characteristics of NMDA receptors contribute to both the specificity and associativity of LTP. For example, when only one group of synaptic inputs is strongly stimulated, LTP is confined to the active synapses (selectivity), since glutamate opens NMDA receptors only at the stimulated sites. However, in terms of associativity, applying a weakly stimulating input current releases glutamate but cannot depolarize the post-synaptic terminal enough to relieve the Mg++ block. When neighboring stimulations are applied to a weak input, these currents work "associatively" to both depolarize and unblock the NMDA receptors on the cell dendrite. | ||
== Recent Findings Implicate Brain-Derived Neurotrophic Factor (BDNF) and Cdc42 GTPase in Theta Burst-Induced "Unsilencing" of Synapses== | |||
Shen et al. (2006) recently analyzed the "unsilencing" of synapses in developing hippocampal cultures. The authors uncover a presynaptic mechanism that allows quick changing of silent synapses to active ones. Although most of the recording pairs display no synaptic responses, brief stimulation with theta bursts was able to functionally activate up to 16% of synapses. In mature cultures, there was a much lower rate of conversion by theta-bursts, suggesting that activation has already occurred at most synapses. The activation of silent synapses was dependent upon NMDA receptors since it was sensitive to APV. Once converted, synapses exhibit both NMDA and AMPA responses. Before synapse activation, however, NMDA responses had not been observed. | |||
The unsilencing was also dependent on endogenous brain-derived neurotrophic factor (BDNF) because incubating with anti-BDNF or blocking signals to the tyrosine kinase B receptor (TrkB, receptor for BDNF) hinders unsilencing. Shen et al. also implicated the small GTPase Cdc42, which is necessary for rearranging cytoskeletal elements in response to activation of tyrosine kinase, in the synapse unsilencing process. General inhibition of small GTPases, as well as a dominant negative inhibition of Cdc42 signaling, blocked the activation of silent synapses in response to theta bursts. However, mature synapses or previously activated synapses were not affected by manipulation of Cdc42 signaling. | |||
==References== | ==References== | ||
Gomperts, SN, Carroll, R, Malenka, RC, et al. (2000) Distinct roles for ionotropic and metabotropic glutamate receptors in the maturation of excitatory synapses. J Neurosci | Bliss, TV and Lomo, T. (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol: 232, 331-56. | ||
Gomperts, SN, Carroll, R, Malenka, RC, et al. (2000) Distinct roles for ionotropic and metabotropic glutamate receptors in the maturation of excitatory synapses. J Neurosci: 20, 2229-37. | |||
Shen, W, Wu, B, Zhang, Z, et al. (2006). Neuron: 50, 401–414. | |||
==<h3>Recent updates to the site</h3>== | ==<h3>Recent updates to the site</h3>== | ||
{{Special:Recentchanges/BIO254&limit=50}} | {{Special:Recentchanges/BIO254&limit=50}} | ||
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