Intrinsic and Sensory Synaptic Properties of Adult Mouse spino-PAG Neurons after Neonatal Tissue Damage

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      While neonatal surgical injury can persistently modulate the excitability of mature lamina I spinoparabrachial neurons, nothing is known about the degree to which early life injury shapes intrinsic firing and synaptic function within adult projection neurons targeting the periaqueductal gray (PAG). The present study seeks to characterize the intrinsic and evoked firing of adult mouse lamina I spino-PAG neurons in the absence or presence of neonatal tissue damage. In vitro whole-cell patch clamp recordings were obtained from retrogradely labelled lamina I spino-PAG neurons in spinal cord slices prepared from adult male and female Gad67-EGFP mice, which were subjected to hindpaw surgical incision (or anesthesia only) at postnatal day (P)3. In response to high-threshold stimulation of the dorsal root, spino-PAG neurons could be even divided into two subtypes based on the evoked action potential (AP) discharge: (1) high-output (HO), defined by repetitive AP discharge throughout the 1 second period following dorsal root stimulation; and (2) low-output (LO), characterized by a single spike or small number of APs restricted to the first 500 ms after the stimulus. Interestingly, there was no significant difference in the overall strength of sensory synaptic drive to HO vs. LO neurons as measured by the area under the primary afferent-evoked EPSCs. Instead, the HO phenotype strongly correlated with the pattern of intrinsic firing evoked by intracellular current injection, as 95% of sampled HO neurons were classified as initial burst or tonic-firing. Finally, P3 incision failed to alter the intrinsic membrane excitability of mature spino-PAG neurons or the efficacy of their primary afferent synaptic inputs. The results demonstrate that sensory afferent-evoked firing of adult spino-PAG neurons is largely governed by their intrinsic membrane properties, and that the excitability of this subpopulation of projection neurons remains stable in the aftermath of neonatal tissue damage. This work was supported by NIH (NS072202 to MLB).
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