In vivo responses of mouse superficial dorsal horn neurones to both current injection and peripheral cutaneous stimulation

Abstract

In the superficial dorsal horn (SDH) processing of noxious and innocuous stimuli is critically dependent on the input-output relationship of its component neurones. Such relationships are routinely examined by assessing neuronal responses to somatic current injection or activation of synaptic inputs. A more complete understanding of input-output relationships would be achieved by comparing, in the same neurone, how the two forms of activation contribute to neuronal output. Therefore, we examined how SDH neurones transform depolarizing current injections and synaptic excitation via peripheral cutaneous stimuli (brush and pinch of the hindpaw) into trains of action potentials, in an in vivo preparation of the adult mouse spinal cord. Under whole-cell current clamp recording conditions four action potential discharge patterns were observed during depolarizing current injection: tonic firing neurones (21/93) discharged spikes throughout the step; initial bursting neurones (35/93) discharged several spikes at step onset; single spiking neurones (16/93) discharged one or two spikes at step onset; and delayed firing neurones (21/93) discharged spikes delayed from the step onset. Four characteristic profiles were observed in response to application of noxious (pinch) and innocuous (brush) cutaneous stimuli: nociceptive neurones (20/37) responded maximally to pinch stimulation; light touch neurones (9/37) responded maximally to brush stimulation; subthreshold neurones (4/37) exhibited depolarizing responses without firing action potentials; and hyperpolarizing neurones (4/37) exhibited a sustained pinch-induced hyperpolarization. Comparisons of current-evoked discharge patterns with peripherally evoked responses indicate SDH neurones expressing each of the four discharge patterns could receive, and therefore participate in the processing of information concerning, either noxious or innocuous stimuli. These data suggest that a neurone's response to current injection does not necessarily help identify or predict how the same neurone will respond to physiologically or functionally relevant stimuli.

Recording Temperature Affects the Excitability of Mouse Superficial Dorsal Horn Neurons, In Vitro

“…Selected data recorded under in vivo conditions are also included for comparative purposes. Some aspects of these data have been reported previously (see Graham et al 2004b). …”

“…S1). 1 When compared with the proportion of SDH neuron discharge profiles encountered in vivo (Graham et al 2004b), both RT and PT proportions showed some similarities. For example, the prevalence of initial bursting neurons at RT is similar to the proportion exhibiting this discharge pattern in vivo.…”

Evidence for a Critical Period in the Development of Excitability and Potassium Currents in Mouse Lumbar Superficial Dorsal Horn Neurons

“…This contrasts with the extensive knowledge of these properties for adult SDH neurons (Graham et al 2004(Graham et al , 2007cLopezGarcia and King 1994;Prescott and De Koninck 2002;Ruscheweyh and Sandkuhler 2002;Ruscheweyh et al 2004; Thomson et al 1989). There has only been one study (in young rats) on the development of intrinsic excitability in SDH neurons (Baccei and Fitzgerald 2005).…”

“…We have used this method in previously published work on adult mouse SDH neurons (Graham et al 2004(Graham et al , 2008. Rheobase current was defined as the smallest step current that would elicit at least one AP.…”

“…We used the mouse for our investigation because of the increasing contribution of this species to our understanding of pain mechanisms (Graham et al 2004;Harvey et al 2004). Our results show significant changes in intrinsic membrane properties, the proportions of action potential (AP) discharge categories, and subthreshold whole cell currents throughout the developmental period examined.…”