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Papers of the Week

Papers: 24 Sep 2022 - 30 Sep 2022

2022 Sep 23


Intrinsic and synaptic properties of adult mouse spino-PAG neurons and the influence of neonatal tissue damage.


The periaqueductal gray (PAG) represents a key target of projection neurons residing in the spinal dorsal horn. In comparison to lamina I spinoparabrachial neurons, little is known about the intrinsic and synaptic properties governing the firing of spino-PAG neurons, or whether such activity is modulated by neonatal injury. Here we address this issue using ex vivo whole-cell patch clamp recordings from lamina I spino-PAG neurons in adult male and female FVB mice following hindpaw incision at postnatal day (P)3. Spino-PAG neurons were classified as high output (HO), medium output (MO) or low output (LO) based on their action potential (AP) discharge following dorsal root stimulation. The HO subgroup exhibited prevalent spontaneous burst-firing and displayed initial burst or tonic patterns of intrinsic firing, while LO neurons showed little spontaneous activity. Interestingly, the level of dorsal root-evoked firing significantly correlated with the resting potential and membrane resistance, but not with the strength of primary afferent-mediated glutamatergic drive. Neonatal incision failed to alter the pattern of monosynaptic sensory input, with the majority of spino-PAG neurons receiving direct connections from low-threshold C-fibers. Furthermore, primary afferent-evoked glutamatergic input and AP discharge in adult spino-PAG neurons were unaltered by neonatal surgical injury. Finally, Hebbian long-term potentiation at sensory synapses, which significantly increased afferent-evoked firing, was similar between P3-incised and naïve littermates. Collectively, these data suggest that the functional response of lamina I spino-PAG neurons to sensory input is largely governed by their intrinsic membrane properties and appears resistant to the persistent influence of neonatal tissue damage.