Long-term potentiation and long-term depression: a clinical perspective

Abstract

Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.

Pharmacological Rescue of Cortical Synaptic and Network Potentiation in a Mouse Model for Fragile X Syndrome

“…Long-term potentiation (LTP) is a well-studied phenomenon shown to mediate synaptic transmission, and is considered to be the cellular model for learning and memory Bliss and Cooke, 2011;Kandel, 2001Kandel, , 2009Neves et al, 2008). LTP has at least two distinct phases: early-phase LTP (E-LTP), which does not need new protein synthesis or transcription, and late-phase LTP (L-LTP), which is transcription and translation related (Abel et al, 1997;Frey et al, 1993;Kandel, 2001Kandel, , 2009).…”

Neurometaplasticity: Glucoallostasis control of plasticity of the neural networks of error commission, detection, and correction modulates neuroplasticity to influence task precision

“…LTP and LTD are dependent on several molecular players including receptors, enzymes, and several signaling molecules such as hormones, neurotransmitters, peptides, and ions [16,17]. The transmitter molecules implicated in LTP and LTD induction include dopamine, glutamate, noradrenaline, serotonin, and acetylcholine [18][19][20]. Growth factors through different modulatory mechanisms also have substantial influence of neurometaplasticity.…”

“…[13,16,36]. The enzymes involved in neurometaplasticity are calmodulin-dependent kinase II (CaMKII), protein kinase A (PKA), protein kinase C (PKC), cAMP-dependent protein kinase (PKA), tyrosine kinase src (Src), mitogen activated protein kinases (MAPK), phospholipases, phosphatidylinositol-3-kinase, among others [16][17][18][19][37][38][39]. Intracellular signaling molecules involved in neurometaplastic events, mediated via induction of LTP and LTD include Ca 2+ , inositol trisphosphate, cAMP-responsive element binding protein (CREB), nuclear factor-kappa-B (NF- [39].…”

Epigenetic regulation of memory: implications in human cognitive disorders

“…Although the effect of these methylation changes on gene expression is not known, this work shows that DNA methylation is plastically regulated in response to neuronal activity. DNA methylation is also altered in the rat hippocampus in response to contextual fear conditioning and induction of long-term synaptic potentiation (LTP) (25,26,28), a form of synaptic plasticity associated with memory (29). Accordingly, knock-out of components of the methylation machinery (Dnmt1 and Dnmt3a) in mice and pharmacological inhibition of DNMTs in the rat hippocampus, results in defects in fear conditioned LTM and hippocampal LTP (25,26,28,30).…”