Synapse density

Woolley CS, McEwen BS (1992) Estradiol mediates fluctuation in hippocampal synapse density during the estrous cycle in the adult rat. J Neurosci 72 2549-2554. 

Beaudoin GM 3rd, Schofield CM, Nuwal T, Zang K, Ullian EM, Huang B, Richardt LF. Afadin, a Ras/Rap effector that controls adherin function, promotes spine and excitatory synapse density in the hippocampus. J Neurosci. 2012 32 99-110. 

Many early studies of transmitter release depended on measuring its concentration in the effluent of a stimulated, perfused nerve/end-organ preparation. This technique is still widely used to study drug-induced changes in noradrenaline release from sympathetic neurons and the adrenal medulla. However, it is important to realise that the concentration of transmitter will represent only that proportion of transmitter which escapes into the perfusate ( overflow ) (Fig. 4.2). Monoamines, for instance, are rapidly sequestered by uptake into neuronal and non-neuronal tissue whereas other transmitters, such as acetylcholine, are metabolised extensively within the synapse. Because of these local clearance mechanisms, the amount of transmitter which overflows into the perfusate will depend not only on the frequency of nerve stimulation (i.e. release rate) but also on the dimensions of the synaptic cleft and the density of innervation. 

Collins S.L., Kunko P.M., Ladenheim B., Cadet J.L., Carroll F.I., Izenwasser S. Chronic cocaine increases kappa-opioid receptor density lack of effect by selective dopamine uptake inhibitors. Synapse. 45 153, 2002. 

The action of catecholamines released at the synapse is modulated by diffusion and reuptake into presynaptic nerve terminals. Catecholamines diffuse from the site of release, interact with receptors and are transported back into the nerve terminal. Some of the catecholamine molecules may be catabolized by MAO and COMT. The cate-cholamine-reuptake process was originally described by Axelrod [18]. He observed that, when radioactive norepinephrine was injected intravenously, it accumulated in tissues in direct proportion to the density of the sympathetic innervation in the tissue. The amine taken up into the tissues was protected from catabolic degradation, and studies of the subcellular distribution of catecholamines showed that they were localized to synaptic vesicles. Ablation of the sympathetic input to organs abolished the ability of vesicles to accumulate and store radioactive norepinephrine. Subsequent studies demonstrated that this Na+- and Cl -dependent uptake process is a characteristic feature of catecholamine-containing neurons in both the periphery and the brain (Table 12-2). 

NMDA and AMPA receptors are spread across the post-synaptic density (PSD), whereas metabotropic glutamate receptors (except mGluR7) are located along the periphery of the PSD (Fig. 15-2). NMDA receptors appear to be present at most or all glutamatergic synapses whereas the content of AMPA receptors is variable - from zero to about 50 receptors per PSD [33]. Some synapses are silent , meaning that activation of them does not elicit AMPA receptor currents when the plasma membrane is hyperpolarized and Mg2+ blocks NMDA receptors. Such silent synapses contain only NMDA receptors. However, AMPA receptors are recruited from the cytosol to the PSD to activate such silent synapses in LTP. 

Tyrosine phosphorylation has a role in the formation of the neuromuscular synapse. For instance, the acetylcholine receptor (AChR) is concentrated at the postsynaptic membrane of the neuromuscular junction at a density of 10,000 receptors/pm2, which is about three orders of magnitude higher than that of the extrasynaptic region... 

Bergersen, L., Waerhaug, O., Helm, J. et al. A novel postsyn-aptic density protein the monocarboxylate transporter MCT2 is co-localized with delta-glutamate receptors in postsynaptic densities of parallel fiber-Purkinje cell synapses. Exp. Brain Res. 136 523-34,2001. 

Developmentally, thyroid hormones interact with sex hormones such that hypothyroidism prolongs the critical period for testosterone-induced defeminization (see below) [3] in contrast, the hyperthyroid state prematurely terminates the sensitivity to testosterone [3]. Undoubtedly, an important link in these and other effects is synapse formation. Hypothyroidism increases synaptic density, at least transiently [3]. Interesting parallels with synapse formation are reported for learning behavior in rats neonatal hypothyroidism impairs learning ability, whereas hyperthyroidism accelerates learning initially, followed by a decline later in life [3]. 

One of the consequences of this rapid increase in protein synthetic capacity in VMN neurons is that E increases the number of spines on dendrites and increases the density of synapses in the VMN. These events occur cyclically during the estrous cycle of the female rat. Dots indicate presynaptic vesicles containing neurotransmitter. 

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... 

Rats exposed to 50 or 250ppmg-cymene 6 hours/day, 5 days/week for 4 weeks had a significantly decreased yield of synaptosomal protein in the brain, suggesting a decrease in the density and total number of synapses. ... 

While much emphasis has been placed on alterations in noradrenergic neurotransmission, TCA drugs are not without effect on serotonin (5-HT) neurotransmission. Long-term studies with TCA drugs in animals have demonstrated postsynaptic supersensitivity to serotonin (5-HTia) receptor agonists at serotonin synapses, with an associated enhancement of serotonergic neurotransmission. The sensitization to 5-HTia agonists is mediated in part by an increase in the density of postsynaptic 5-HTia receptors. Enhancement of trans-... 

Similar to axons, synapses are initially overproduced in the infant primate, reaching their maximum number during infancy (2-4 months of age) (Rakic et ah, 1986). Cortical synapses are eventually pruned down to a density of approximately 15 to 20 synapses/100 lm of neuropil. Axons and synapses are eliminated through different time courses (Fig. 1.7). In primates, the adult number of synapses in the primate cerebral cortex is not achieved until near adolescence (Rakic et ah, 1986). 

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