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Long-term depression (LTD), in neurophysiology
Neurophysiology

Neurophysiology is a part of physiology. Neurophysiology is the study of nervous system function. Primarily, it is connected with neurobiology, psychology, neurology, clinical neurophysiology, electrophysiology, ethology, neuroanatomy, cognitive science and other brain sciences....
, is the weakening of a neuronal synapse that lasts from hours to days. It results from either strong synaptic stimulation (as occurs in the cerebellar
Cerebellum

The cerebellum is a region of the brain that plays an important role in the integration of perception, coordination and motoneuron control. In order to coordinate motor control, there are many neural pathways linking the cerebellum with the cerebrum motor cortex and the spinocerebellar tract ....
 Purkinje cell
Purkinje cell

For the cells of the electrical conduction system of the heart, see Purkinje fibersPurkinje cells, or Purkinje neurons, are a class of GABAergic neurons located in the cerebellum....
s) or persistent weak synaptic stimulation (as in the hippocampus
Hippocampus

The hippocampus is a brain structure located inside the medial temporal lobe of the cerebral cortex, and therefore is part of the telencephalon ....
). Long-term potentiation
Long-term potentiation

In neuroscience, long-term potentiation is the long-lasting improvement in communication between two neurons that results from stimulating them simultaneously....
 (LTP) is the opposing process. LTD is thought to result from changes in postsynaptic receptor
Receptor (biochemistry)

In biochemistry, a receptor is a protein molecule, embedded in either the plasma membrane or cytoplasm of a cell, to which a mobile signaling molecule may attach....
 density, although changes in presynaptic release may also play a role.






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Long-term depression (LTD), in neurophysiology
Neurophysiology

Neurophysiology is a part of physiology. Neurophysiology is the study of nervous system function. Primarily, it is connected with neurobiology, psychology, neurology, clinical neurophysiology, electrophysiology, ethology, neuroanatomy, cognitive science and other brain sciences....
, is the weakening of a neuronal synapse that lasts from hours to days. It results from either strong synaptic stimulation (as occurs in the cerebellar
Cerebellum

The cerebellum is a region of the brain that plays an important role in the integration of perception, coordination and motoneuron control. In order to coordinate motor control, there are many neural pathways linking the cerebellum with the cerebrum motor cortex and the spinocerebellar tract ....
 Purkinje cell
Purkinje cell

For the cells of the electrical conduction system of the heart, see Purkinje fibersPurkinje cells, or Purkinje neurons, are a class of GABAergic neurons located in the cerebellum....
s) or persistent weak synaptic stimulation (as in the hippocampus
Hippocampus

The hippocampus is a brain structure located inside the medial temporal lobe of the cerebral cortex, and therefore is part of the telencephalon ....
). Long-term potentiation
Long-term potentiation

In neuroscience, long-term potentiation is the long-lasting improvement in communication between two neurons that results from stimulating them simultaneously....
 (LTP) is the opposing process. LTD is thought to result from changes in postsynaptic receptor
Receptor (biochemistry)

In biochemistry, a receptor is a protein molecule, embedded in either the plasma membrane or cytoplasm of a cell, to which a mobile signaling molecule may attach....
 density, although changes in presynaptic release may also play a role. Cerebellar LTD has been hypothesized to be important for motor learning
Motor learning

Motor learning is the process of improving the motor skills, the smoothness and accuracy of movements. It is obviously necessary for complicated movements such as Speech communication, playing the piano and climbing trees, but it is also important for calibrating simple movements like reflexes, as parameters of the body and environment chang...
. 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.

Calcium influx in a neuron can cause both LTP and LTD, depending on the timing and frequency of the input (Dudek & Bear 1992) The Bienenstock, Cooper and Munro model
BCM theory

BCM theory, BCM synaptic modification, or the BCM rule, named for Elie Bienenstock, Leon Cooper, and Paul Munro, is a physical theory of learning in the visual cortex developed in 1981....
 (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
Action potential

An action potential is a self-regenerating wave of electrochemical activity that allows nerve cells to carry a signal over a distance. It is the primary electrical signal generated by nerve cells, and arises from changes in the permeability of the nerve cell's axonal Cell membranes to specific ions....
, 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 3
Calcineurin

Calcineurin is a protein phosphatase also known as protein phosphatase 3, PPP3CA, and formerly known as protein phosphatase 2B . Calcineurin activates NFATC1 , a transcription factor by dephosphorylation it....
 play the same role in LTD as CaMKII
Ca2+/calmodulin-dependent protein kinase

Ca2+/calmodulin-dependent protein kinases or CaM kinases are serine/threonine-specific protein kinases that are primarily regulated by the Ca2+/calmodulin complex....
 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

  • Hebbian theory
    Hebbian theory

    Hebbian theory describes a basic mechanism for synaptic plasticity wherein an increase in synapse efficacy arises from the presynaptic cell's repeated and persistent stimulation of the postsynaptic cell....
  • BCM theory
    BCM theory

    BCM theory, BCM synaptic modification, or the BCM rule, named for Elie Bienenstock, Leon Cooper, and Paul Munro, is a physical theory of learning in the visual cortex developed in 1981....
  • Excitatory postsynaptic potential
    Excitatory postsynaptic potential

    In neuroscience, an excitatory postsynaptic potential is a temporary depolarization of postsynaptic membrane potential caused by the flow of positively charged ions into the postsynaptic cell as a result of opening of ligand-sensitive channels....
  • Homeostatic plasticity
    Homeostatic plasticity

    In Neuroscience, homeostatic plasticity refers to the capacity of neurons to regulate their own excitability relative to network activity, a compensatory adjustment that occurs over the timescale of days....
  • Inhibitory postsynaptic potential
    Inhibitory postsynaptic potential

    An inhibitory postsynaptic potential is a synaptic potential that decreases the chance that a future action potential will occur in a postsynaptic neuron or a-motoneuron....
  • Long-term potentiation
    Long-term potentiation

    In neuroscience, long-term potentiation is the long-lasting improvement in communication between two neurons that results from stimulating them simultaneously....
     (LTP)
  • Long-term depression
    Long-term depression

    Long-term depression , in neurophysiology, is the weakening of a neuronal synapse that lasts from hours to days. It results from either strong synapse stimulation or persistent weak synaptic stimulation ....
     (LTD)
  • Spike timing dependent plasticity
    Spike timing dependent plasticity

    Spike-timing-dependent plasticity is a general term for functional changes in neurons and at synapses that are sensitive to the timing of action potentials in connected neurons....
     (STDP)
  • Neural Facilitation
    Neural facilitation

    In neuroscience, neural facilitation, also known as paired pulse facilitation, is the increase in postsynaptic potential evoked by a second impulse....
     (Short-term plasticity)
  • Neuroplasticity
    Neuroplasticity

    Neuroplasticity refers to changes that occur in the organization of the brain as a result of experience. The coining of the term plasticity in regards to neuronal process is attributed to Polish neuroscientist Jerzy Konorski....
  • Postsynaptic potential
    Postsynaptic potential

    Postsynaptic potentials are changes in the membrane potential of the postsynaptic terminal of a chemical synapse. Postsynaptic potentials are membrane potential, and should not be confused with action potentials although their function is to initiate or inhibit action potentials....