Intrinsic and synaptic properties of adult mouse spinoperiaqueductal gray neurons and the influence of neonatal tissue damage

Abstract

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. In this study, this issue was addressed using ex vivo whole-cell patch clamp recordings from lamina I spino-PAG neurons in adult male and female FVB mice after hindpaw incision at postnatal day (P)3. Spino-PAG neurons were classified as high output, medium output, or low output based on their action potential discharge after dorsal root stimulation. The high-output subgroup exhibited prevalent spontaneous burst firing and displayed initial burst or tonic patterns of intrinsic firing, whereas low-output 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 most spino-PAG neurons receiving direct connections from low-threshold C-fibers. Furthermore, primary afferent-evoked glutamatergic input and action potential 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 naive 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.

In Brief

The intrinsic membrane properties and primary afferent synaptic inputs that govern the firing of adult lamina I spino-periaqueductal gray neurons are unaffected by neonatal tissue damage.