Synaptic plasticity

Tolerance to morphine is a further form of synaptic plasticity in which NO may be involved. The mechanisms of morphine tolerance are poorly understood, but glutamate acting at NMDA receptors is probably involved, because development of tolerance can be inhibited by NMDA antagonists. It has recently been shown that NOS inhibitors given with morphine completely prevent tolerance without affecting the actions of morphine itself, suggesting a selective effect on the tolerance mechanism. 

In the case of NMDA receptors Ca permeability is also an important issue and is a key to understanding certain forms of glutamate mediated synaptic plasticity (see below). These properties of NMDA receptors can be readily observed through 

In addition to ligand gated ion channels neurotransmitters often activate GPCRs. These receptors are all based on a structural motif in which the receptor protein crosses the membrane 7 times in a serpentine like manner so that that N-terminal is extracellular and the C-terminal is intracellular. This arrange- 

Acknowledgment. The authors thank William Wassom, Graphic Designer at the University of Nebraska Medical Center for his assistance wtith the figures. 

Tlie undershoot of an action potential occurs from 

Tlie resting membrane potential is lai gely influenced by 

What is a selectivity filter of an ion channel Do all channels contain a selectivity fitter  

How many pore-forming K channel subunits assemble to form a functional channel  

The mechanisms underlying post-tetanic and frequency potentiation have long been of interest to neurobiologists for their possible implications 

Isolated brain slice preparations have also become of great interest to those investigating the mechanisms of action of drugs and putative transmitter agents by microiontophoresis (Ryall and Kelly, 1978). 

Indeed Brown and Constant (1980) have recently taken this argument one step further and suggested that one might calculate the extra current (A/) induced to flow across the cell membrane by the presence of the particular transmitter. According to the model proposed above. 

A depolarizing ramp is a convenient way of monitoring neuronal excitability, since it does not involve changes in the excitability of adjacent cells, such as those occur during electrical stimulation of synaptic pathways. 

---

T No A PKA Brain (neuron), adrenal (medulla) Neurotransmission, synaptic plasticity, LTP, memory,circadian rhythm... 

T No A No A PKA t PKC Brain, lung, skeletal muscle Synaptic plasticity, arrest of cell proliferation... 

Long-term depression (LTD) is a synaptic plasticity phenomenon that corresponds to a decrease in the synaptic strength (decrease in the post-synaptic response observed for the same stimulation of the pre-synaptic... 

Long-term potentiation (LTP) is a synaptic plasticity phenomenon that corresponds to an increase in the synaptic strength (increase in the post-synaptic response observed for the same stimulation of the presynaptic terminals) observed after a high frequency stimulation (tetanus) of the afferent fibres. This increased response is still observed hours and even days after the tetanus. The phenomenon is often observed at glutamatergic synapses and involves, in most cases, the activation of the V-methyl D-aspartate (NMDA) subtype of ionotropic glutamate receptors. 

Herz J, Chen Y (2006) Reelin, lipoprotein receptors and synaptic plasticity. Nat Rev 7 850-859... 

NMDAR. An ionotropic receptor for glutamate. It plays a critical role in synaptic plasticity mechanisms and thus is necessary for several types of learning and memory. 

Colingridge, G and Singer, W (1990) Excitatory amino acid receptors and synaptic plasticity. Trends Pharm. Sci. 11 290-296. 

Matsuoka M., Kaba H., Mori Y. and Ichikawa M. (1997). Synaptic plasticity in olfactory memory formation in female mice. Neurorep 8, 2501-2504. 

Lasley SM University of Illinois, Peoria, 111 Pb-induced alterations of the glutamate-mediated regulation of intracellular Ca+2 concentrations and synaptic plasticity in hippocampal neurons (rats) National Institute of Environmental Health Sciences... 

Noradrenaline acts on three types of receptor. The ai receptors mediate the main excitatory effects of noradrenaline upon wake-active neurons in the dorsal raphe, basal forebrain, and elsewhere (Vandermaelen Aghajanian, 1983 Nicoll, 1988 Fort et al., 1995 Brown et al., 2002). The a2 receptors mediate inhibitory effects of noradrenaline, e.g. on noradrenaline neurons themselves and on cholinergic brainstem neurons (Williams et al., 1985 Williams Reiner, 1993). The (3-receptors modulate neurons in a more subtle fashion, increasing excitability via blockade of afterhyperpolarizations in hippocampal and cortical neurons (Haas Konnerth, 1983). Activation of (3-receptors also promotes synaptic plasticity via activation of the cyclic-AMP-dependent kinase (PKA) and cyclic AMP response element binding protein (CREB) signal transduction pathway (Stanton Sarvey, 1987 Cirelli et al., 1996). 

Sweatt, J.D. Mitogen-activated protein kinases in synaptic plasticity and memory. Curr. Opin. Neu-robiol. 14 311, 2004. 

Jones, S., Bonci, A. Synaptic plasticity and drug addiction. Curr. Opin. Pharmacol. 5 20, 2005. 

Sutton, M. A., and Schuman, E. M. (2006). Dendritic protein synthesis, synaptic plasticity, and memory. Cell 127, 49-58. 

We utilized this technique to analyze Scrapper gene-dehcient (SCR-KO) mice.21 SCRAPPER, a protein that we have recently reported, is localized at synapses in neurons. It is a ubiquitin E3 ligase that is involved in the decomposition of RIM (Rab3-interacting molecule) 1, an important regulator of synaptic plasticity, and thus regulates synaptic transmissions.22... 

A variety of different types of tissue preparation are used to study neurosecretion and synaptic transmission. A classical preparation is the frog NMJ (discussed below). The brain slice has been used for many years for biochemical studies of CNS metabolism and is a useful preparation for electrophysiological studies of synaptic transmission in the CNS. Slices can be oriented to maintain the local neuronal circuitry and can be thin, 0.3 mm, to minimize anoxia. The transverse hippocampal slice is widely used as an electrophysiological preparation to study synaptic plasticity (see Ch. 53). Primary cultures of neurons from selected CNS areas and sympathetic ganglia are also frequently used. They permit excellent visual identification of individual neurons and control of the extracellular milieu, but the normal neuronal connections are disrupted. 

---