Noise or signal? Spontaneous activity of dorsal horn neurons: patterns and function in health and disease

Abstract

Spontaneous activity refers to the firing of action potentials by neurons in the absence of external stimulation. Initially considered an artifact or "noise" in the nervous system, it is now recognized as a potential feature of neural function. Spontaneous activity has been observed in various brain areas, in experimental preparations from different animal species, and in live animals and humans using non-invasive imaging techniques. In this review, we specifically focus on the spontaneous activity of dorsal horn neurons of the spinal cord. We use a historical perspective to set the basis for a novel classification of the different patterns of spontaneous activity exhibited by dorsal horn neurons. Then we examine the origins of this activity and propose a model circuit to explain how the activity is generated and transmitted to the dorsal horn. Finally, we discuss possible roles of this activity during development and during signal processing under physiological conditions and pain states. By analyzing recent studies on the spontaneous activity of dorsal horn neurons, we aim to shed light on its significance in sensory processing. Understanding the different patterns of activity, the origins of this activity, and the potential roles it may play, will contribute to our knowledge of sensory mechanisms, including pain, to facilitate the modeling of spinal circuits and hopefully to explore novel strategies for pain treatment.

Keywords: Firing pattern; Sensory processing; Spike trains; Spinal cord.

Fig. 1

Previous classification of spontaneous firing patterns. Idealized inter-spike intervals (ISI) and auto-correlograms corresponding to the different patterns of spontaneous activity proposed by Brown et al. (1979) [14]. Graphs from real data can be found in the original publication. a Poisson-like distribution with a flat auto-correlogram. b and c Poisson-like correlograms with initial peaks. d and e Gaussian distributions and different degrees of regularity. f Bimodal frequency distribution and auto-correlogram of a neuron firing bursts at regular intervals

Fig. 2

Single spike patterns. a shows an irregular pattern with single spikes. The original recording from a MEA is shown in the left lower panel. The corresponding instantaneous frequency (Inst. Freq) is shown above. Graphs to the right and far right show ISI distribution and auto-correlogram for this neuron. b shows a regular pattern with single spikes. Panels arranged as in (a)

Fig. 3

Fast burst patterns. Irregular (a) and regular (b) fast burst patterns from two dorsal horn neurons. Original extracellular recordings and graphs arranged as in Fig. 2. Middle panels show duplets fired by each neuron. Insets in ISI and auto-correlogram graphs in (b) show early peaks generated by the second spike of the duplet

Fig. 4

Slow burst patterns. Irregular (a) and regular (b) slow burst patterns from two different dorsal horn neurons. Original extracellular recordings and graphs arranged as in previous figures. Middle panels show bursts produced by each neuron

Fig. 5

Mixed burst patterns. Irregular (a) and regular (b) mixed burst patterns from two different dorsal horn neurons. Original extracellular recordings and graphs arranged as in previous figures. Middle panels show bursts produced by each neuron. Note the initial high firing frequency and the progressive decay

Fig. 6

Intracellular records of neurons with spontaneous activity. Figure shows basic electrophysiological properties of three neurons with spontaneous activity recorded from spinal cord slices of adult mice with whole cell recording techniques. Original recordings are shown for neurons with irregular single spike (a), regular single spike (b), and irregular fast burst firing (c). Long unperturbed recordings are shown in the upper-left panels, followed by time expanded segments of the recordings marked by black triangles in the left. Resting membrane potential is indicated by dotted lines. Auto-correlograms are included below the original recordings to illustrate the firing pattern. Finally, responses to positive and negative current injection pulses are show for each neuron. Traces below the voltage recordings indicate the current intensity applied (calibration bars 100 pA; 200 ms). Graphs in (d) show a quantification of the voltage responses to negative current pulses measured at the maximum deflection for the three neurons (lower-left) and the action potential (Action Pot.) firing in response to positive current injections (upper-right)

Fig. 7

Proposed arrangement of neurons in the dorsal horn to explain the origin and spread of spontaneous activity in the cord. A generator ensemble of neurons (blue) provides synaptic input to an effector ensemble (orange) that excites primary afferents. Both generator and effector ensembles are influenced by descending and intraspinal modulation. Finally, primary afferents spread excitation to an ensemble of postsynaptic neurons formed by projection neurons and interneurons. IS Irregular single spike, IFB irregular fast burst, ISB irregular slow burst, RS regular single spike, RSB regular slow burst