Long-term depression 487921 213503249 2008-05-19T17:10:06Z Neelix 1169106 Added other distinguishing link {{confuse|chronic depression|Long Depression}} '''Long-term depression''' (LTD), in [[neurophysiology]], is the weakening of a neuronal [[synapse]] that lasts from hours to days. It results from either strong [[synapse|synaptic]] stimulation (as occurs in the [[cerebellum|cerebellar]] [[Purkinje cell]]s) or persistent weak synaptic stimulation (as in the [[hippocampus]]). [[Long-term potentiation]] (LTP) is the opposing process. LTD is thought to result from changes in postsynaptic [[receptor (biochemistry)|receptor]] density, although changes in presynaptic release may also play a role. Cerebellar LTD has been hypothesized to be important for [[motor learning]]. However, it is likely that other plasticity mechanisms play a role as well. Hippocampal LTD may be important for the clearing of old memory traces. Hippocampal/cortical LTD can be dependent of NMDA receptors, metabotrophic glutamate receptors (mGluR) or endocannabinoids. LTD is distinct from synaptic depotentiation, which is the reversal of long-term potentiation (Barrionuevo 1980). LTD is a novel reduction in synaptic strength - specifically, an activity-dependent reduction in the excitatory post-synaptic potential compared to the baseline level. Questions: How can a similar calcium influx cause both LTP and LTD? It depends on the timing and frequency of the input (Dudek & Bear 1992) The Bienenstock, Cooper and Munro model (BCM model - 1982) explains how the type of Ca2+ signal leads to both LTP and LTD. They postulate that when there is a low calcium influx, it leads to LTD, and a Ca2+ entry above threshold leads to LTP. The threshold level is on a sliding scale, and depends on the history of the synapse. If the synapse has already been subject to LTP, the threshold is raised, increasing the probability that a calcium influx will yield LTD. In this way, it provides a "negative feedback" system to maintain synaptic plasticity. Frequency of the stimulus is another factor for the LTP/LTD switch. Using single spike timing dependent plasticity methods (STDP), it was shown that LTP is induced when the neurotransmitter release occurs 5-15ms '''before''' a back-propagating [[action potential]], and LTD is induced when the stimulus occurs 5-15ms '''after''' the bAP. (Markram et al 1997, Kennedy 2005) There is a plasticity window: if the pre-synaptic and post-synaptic spikes are too far apart (i.e. more than 15ms apart), there is little chance of plasticity (Bi & Poo 1998). The possible window for LTD is wider than that for LTP (Feldmann 2000) - although note that this threshold depends on synaptic history. According to the Lisman model, [[protein phosphatase]] 1 and 2B play the same role in LTD as [[Ca2+/calmodulin-dependent protein kinase|CaMKII]] does in LTP, but is activated at lower calcium levels and thus provide a mechanism to induce LTD at low calcium levels and LTP at high calcium levels. == See also == *[[Long-term potentiation]] [[Category:Neurophysiology]] {{neuroscience-stub}} [[de:Langzeit-Depression]] [[it:Long Term Depression]] [[zh:长期抑势]]