Loss of Long-Term Depression in the Insular Cortex after Tail Amputation in Adult Mice

Abstract

The insular cortex (IC) is an important forebrain structure involved in pain perception and taste memory formation. Using a 64-channel multi-electrode array system, we recently identified and characterized two major forms of synaptic plasticity in the adult mouse IC: long-term potentiation (LTP) and long-term depression (LTD). In this study, we investigate injury-related metaplastic changes in insular synaptic plasticity after distal tail amputation. We found that tail amputation in adult mice produced a selective loss of low frequency stimulation-induced LTD in the IC, without affecting (RS)-3,5-dihydroxyphenylglycine (DHPG)-evoked LTD. The impaired insular LTD could be pharmacologically rescued by priming the IC slices with a lower dose of DHPG application, a form of metaplasticity which involves activation of protein kinase C but not protein kinase A or calcium/calmodulin-dependent protein kinase II. These findings provide important insights into the synaptic mechanisms of cortical changes after peripheral amputation and suggest that restoration of insular LTD may represent a novel therapeutic strategy against the synaptic dysfunctions underlying the pathophysiology of phantom pain.

Neonatal Maternal Deprivation Enhances Presynaptic P2X7 Receptor Transmission in Insular Cortex in an Adult Rat Model of Visceral Hypersensitivity

“…IC is involved in peripheral nerve ligation‐induced neuropathic pain , CFA‐induced hyperalgesia , phantom limb pain of human , but not in acute pain . In the present study, although the expression of P2X7Rs upregulated in both hemispheres of IC, microinjection of P2X7R agonist into right IC was efficient to induce visceral hypersensitivity in control rats and microinjection of P2X7R antagonist reversed CVH in NMD rats.…”

Characterization of short- and long-term mechanical sensitisation following surgical tail amputation in pigs

“…Long-term synaptic depression in the insular cortex has been previously characterised in mice as a consequence of tail amputation 38 , supporting the hypothesis of central sensitisation following a peripheral injury. In order to confirm whether peripheral mechanical sensitisation is a valid proxy measure for the experience of pain in pigs, more comprehensive experimental approaches would be required, coupling quantitative sensory testing with more complex behavioural non-reflexive assays (e.g.…”

The analgesic and anti‐inflammatory effects of Salvinorin A analogue β‐tetrahydropyran Salvinorin B in mice

“…A simplified up-down method was used (Bonin et al, 2014), where a positive response resulted in the use of next lower filament in the subsequent test; if no response was observed, the next higher filament was used. This continued until 5 filaments had been administered and the final threshold was calculated as previously described (Bonin et al, 2014). A positive response was defined as a sharp withdrawal of the paw upon application or removal of the filament.…”