Scientific Understanding of Consciousness
Consciousness as an Emergent Property of Thalamocortical Activity

Gliogenic LTP spreads widely in nociceptive pathways


Science  02 Dec 2016: Vol. 354, Issue 6316, pp. 1144-1148

Gliogenic LTP spreads widely in nociceptive pathways

M. T. Kronschläger,

Department of Neurophysiology, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 Vienna, Austria.


Learning and memory formation involve long-term potentiation (LTP) of synaptic strength. A fundamental feature of LTP induction in the brain is the need for coincident pre- and postsynaptic activity. This restricts LTP expression to activated synapses only (homosynaptic LTP) and leads to its input specificity.

In the spinal cord, we discovered a fundamentally different form of LTP that is induced by glial cell activation and mediated by diffusible, extracellular messengers, including d-serine and tumor necrosis factor (TNF), and that travel long distances via the cerebrospinal fluid, thereby affecting susceptible synapses at remote sites. The properties of this gliogenic LTP resolve unexplained findings of memory traces in nociceptive pathways and may underlie forms of widespread pain hypersensitivity.

Activity-dependent, homosynaptic long-term potentiation (LTP)    at synapses in nociceptive pathways     contributes to pain amplification (hyperalgesia) at the site of an injury or inflammation. Homosynaptic LTP can, however, not account for pain amplification at areas surrounding (secondary hyperalgesia) or remote from (widespread hyperalgesia) an injury. It also fails to explain hyperalgesia that is induced independently of neuronal activity in primary afferents—e.g., by the application of or the withdrawal from opioids (opioid-induced hyperalgesia).    Glial cells are believed to contribute to these forms of hyperalgesia    and to LTP in nociceptive pathways.

Gliogenic LTP is a new form of paracrine synaptic plasticity in the central nervous system and may lead to pain amplification close to and remote from an injury or an inflammation. This is in line with the concept of chronic pain as a gliopathy involving neurogenic neuroinflammation. These new insights may pave the way for novel pain therapies. P2X7Rs play a key role in chronic inflammatory and neuropathic pain and in other neurodegenerative and neuropsychiatric disorders. Glial cells display considerable diversity between and within distinct regions of the central nervous system. If the presently identified gliogenic LTP also existed at some brain areas, it could be of relevance not only for pain but also for other disorders, such as cognitive deficits, fear and stress disorders, and chronic immune-mediated diseases.

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