Abstract
Parvalbumin-expressing interneurons (PVINs) in the spinal dorsal horn are found primarily in laminae II inner and III. Inhibitory PVINs play an important role in segregating innocuous tactile input from pain-processing circuits through presynaptic inhibition of myelinated low-threshold mechanoreceptors and postsynaptic inhibition of distinct spinal circuits. By comparison, relatively little is known of the role of excitatory PVINs (ePVINs) in sensory processing. Here, we use neuroanatomical and optogenetic approaches to show that ePVINs comprise a larger proportion of the PVIN population than previously reported and that both ePVIN and inhibitory PVIN populations form synaptic connections among (and between) themselves. We find that these cells contribute to neuronal networks that influence activity within several functionally distinct circuits and that aberrant activity of ePVINs under pathological conditions is well placed to contribute to the development of mechanical hypersensitivity.
Highlights
The dorsal horn of the spinal cord plays a key role in gating and modulating sensory input originating from primary afferents before it is relayed to supraspinal sites for perception
We found anatomical evidence for excitatory synaptic inputs derived from excitatory PVINs (ePVINs) onto both Inhibitory PVINs (iPVINs) and ePVINs (Figures 3A and 3B, respectively), and of inhibitory synaptic inputs from iPVINs onto both iPVINs and ePVINs (Figures 3C and 3D, respectively)
D depolarisation (PAD) that is capable of eliciting neurotransmitter release from afferent E terminals [8]. This mechanism would produce longer latency polysynaptic optically evoked excitatory postsynaptic currents (oEPSCs) as we have previously demonstrated in iPVIN photostimulation responses recorded in lamina II
Summary
The dorsal horn of the spinal cord plays a key role in gating and modulating sensory input originating from primary afferents before it is relayed to supraspinal sites for perception. Disinhibition unmasks polysynaptic excitatory PVIN circuits and recruits postsynaptic targets The combined observations that ePVIN inputs rarely evoked AP discharge, but that this circuitry was under ongoing inhibitory regulation, prompted additional photostimulation experiments under disinhibited conditions (Figure 8A) These recordings were undertaken in the presence of bicuculline (10 M) and strychnine (1 M) to block inhibition and PADevoked excitation arising from iPVINs, allowing excitatory inputs and the postsynaptic. C Comparison of oEPSC1 and oEPSC2 latencies with the latency of AP discharge in Acorresponding recordings (3.10 ± 0.15 ms vs 20.26 ± 3.08 ms vs 26.78 ± 6.15 ms) shows that the onset of postsynaptic spiking was delayed relative to the timing of photostimulation (Figure 8D) This relationship is compatible with postsynaptic spiking driven largely through ePVIN mediated polysynaptic pathways, rather than monosynaptic input from ePVINs. Postsynaptic targets of PVIN circuits Given the substantial heterogeneity described for dorsal horn neurons [32; 76] we assessed the AP discharge patterns of neurons receiving oEPSCs (n = 203, Figure 9) as these features have been used to infer inhibitory or excitatory neuron phenotype [32; 76]. The presence of bicuculline-insensitive oEPSCs (3/6) implies that polysynaptic input to PNs is mediated by ePVINs (Figure 10C, upper)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
