Long-Term Depression

Long-term depression (LTD) has been found to be an important part of motor learning in the hippocampus and the cerebellum. The two ways in which LTD occur are via homosynaptic plasticity and heterosynaptic plasticity. Homosynaptic LTD is activated at the level of a singular synapse where it is receiving activation from a very low frequency stimulus. In contrast to homosynaptic LTD, where neurons must be activated directly and the synaptic weakening happens within the same neuron, heterosynaptic plasticity is instead based on the levels of Ca²⁺ and will only impact neurons that are inactive or are being influenced by the activation of neurons next to them, not directly upon them (Bear, 1995).

LTD in the Hippocampus

Synapses between Shaffer collaterals and CA1 pyramidal cells are impacted by how much and how often Ca²⁺ is brought into the cell. When receiving constant stimulation for a long time (about 10 minutes) as well as low frequency stimulation (about 1 Hz), a negative feedback system is created to maintain the integrity of the synapse that was created. To make this work,  LTD is dependent on whether a cell is undergoing long-term potentiation (LTP). After a while of undergoing LTP, a cell will switch to LTD when the amount of Ca²⁺ entering the cell triggers the creation of NMDA-type glutamate receptors. Calcium-dependent phosphatases dephosphorylate AMPA receptors, which causes them to move away from the the postsynaptic cleft, decreasing the cell’s sensitivity to glutamate.

LTD in the Cerebellum

Parallel fibers and climbing fibers are responsible for excitatory input to cerebellar Purkinje neurons. When both parallel fibers and climbing fibers are activated, LTD can occur (Hoxha, 2016). This is done by depolarization of the membrane through the binding of glutamate to metabotropic receptors. In quick succession, phospholipase C is activated to produce inositol triphosphate and diacylglycerol, which augment the calcium concentration by releasing calcium from intracellular stores. Protein kinase C phosphorylates AMPA receptors, which causes them to internalize (move inward into the cell) and the neuron to be less sensitive to glutamate.

Endocannabinoids

Substance Use and Plasticity