Postsynaptic components

Plate 6 Schematic of the prototypical dopaminergic synapse. Pre- and postsynaptic components of a dopaminergic synapse summarizing molecular pathways for dopamine synthesis, metabolism, and second messenger effects following Dl-like or D2-like receptor activation. 

A neurally derived signaling protein, agrin, acts through a receptor tyrosine kinase, MuSK, in the formation of the specialized postsynaptic endplate by interaction with rapsyn. Thus, MuSK-rapsyn interactions are critical in forming the local scaffold for postsynaptic components in the motor endplate [43,44]. 

Measuring muscle-evoked responses to repetitive motor nerve electrical stimulation permits detection of presyn-aptic neuromuscular junction dysfunction. In botulism and the Lambert-Eaton syndrome, repetitive stimulation elicits a smaller than normal skeletal muscle response at the beginning of the stimulus train, due to impaired initial release of acetylcholine-containing vesicles from presyn-aptic terminals of motor neurons followed by a normal or accentuated incremental muscle response during repeated stimulation. This incremental response to repetitive stimulation in presynaptic neuromuscular disorders can be distinguished from the decremental response that characterizes autoimmune myasthenia gravis, which affects the postsynaptic component of neuromuscular junctions. 

Typically, the presynaptic ending is further distinguished from the postsynaptic component by the conspicuous presence of neurotransmitter-filled vesicles. In response to presynaptic membrane depolarization, the vesicles exocytose their contents into the cleft through complicated membrane-trafficking events. The presynaptic axon terminal (bouton) of the presynaptic component also contains other organelles such as mitochondria, smooth endoplasmic reticulum, microtubules, and neurofilaments. The presynaptic membrane is variably populated by docking/fusion apparatus, ion channels, and other protein constituents. The 20-30 nM wide synaptic cleft separates the pre- and postsynaptic membranes and generally contains a dense plaque of intercellular material that includes microfilaments. 

Rao A, Cha EM, Craig AM. 2000. Mismatched appositions of presynaptic and postsynaptic components in isolated hippocampal neurons. J. Neurosci. 20 8344-53... 

Wu YY, Wang X, Tan L, Liu D, Liu XH, Wang Q et al (2013) Lithium attenuates scopolamine-induced memory deficits with inhibition of GSK-3P and preservation of postsynaptic components. J Alzheimers Dis 37(3) 515-527... 

NMJs at type IIx and/or Ilb fibers. Moreover, the extent of overlap between pre- and postsynaptic components of the NMJ was lower at type I muscle fibers in hypothyroid compared to control animals. No studies have specifically examined the effects of hypothyroidism (either as a result of low-iodine diets or other conditions) on the ultrastructure of NMJs or the size of synaptic vesicle pools. 

Acetylcholinesterase is a component of the postsynaptic membrane of cholinergic synapses of the nervous system in both vertebrates and invertebrates. Its structure and function has been described in Chapter 10, Section 10.2.4. Its essential role in the postsynaptic membrane is hydrolysis of the neurotransmitter acetylcholine in order to terminate the stimulation of nicotinic and muscarinic receptors (Figure 16.2). Thus, inhibitors of the enzyme cause a buildup of acetylcholine in the synaptic cleft and consequent overstimulation of the receptors, leading to depolarization of the postsynaptic membrane and synaptic block. 

Once THC is bound to presynaptic and postsynaptic receptor sites, a way to stop its action is required. Otherwise, stimulation could continue indefinitely and a perpetual high could be maintained from just a few puffs of marijuana. Research has shown that the endogenous cannabinoid anandamide is deactivated by being removed from receptors and transported into the cell, where it is broken down by an enzyme into nonactive components. This process is believed to be the same for THC. 

Both NMDA and AMPA receptor components of excitatory postsynaptic potentials (EPSPs) are produced by the brief (1 ms) appearance of free transmitter in the synaptic cleft (Fig 15-10A). Synaptically released glutamate thus... 

Finally, this section has focused almost entirely on axonal transport, but dendritic transport also occurs [25]. Since dendrites usually include postsynaptic regions while most axons terminate in presynaptic elements, the dendritic and axonal transport each receive a number of unique proteins. An added level of complexity for intraneuronal transport phenomena is the intriguing observation that mRNA is routed into dendrites where it is implicated in local protein synthesis at postsynaptic sites, but ribosomal components and mRNA are largely excluded from axonal domains [26]. Regulation of protein synthesis in dendritic compartments is an important mechanism is synaptic plasticity [27,28]. The importance of dendritic mRNA transport and local protein synthesis is underscored by the demonstration that the mutation associated with Fragile X syndrome affects a protein important for transport and localization of mRNA in dendrites [27, 29], Similar processes of mRNA transport have been described in glial cells [30]. 

NMDA receptors are anchored in the postsynaptic density (PSD95, 95 kDa), a complex with which over 80 proteins have been associated (see Ch. 15). Postmortem studies have examined the expression of the subunits of the NMDA receptors as well as components of the PSD [29]. In one study in the thalamus, the NR1 and NR2B subunits were decreased in schizophrenia and PSD95, SAP102 (Synapse Associated Protein kDa 102) and NF-L (Neurofilament-Light), components of the PSD, were also significantly reduced with the latter reduction also found in bipolar disorder. Similarly, other studies have shown... 

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