Ground truth construction and parameter tuning for the detection of sleep spindle timing in rodents.

BACKGROUND: The precise detection of cortical sleep spindles is critical to basic research on memory consolidation in rodents. Previous research using automatic spindle detection algorithms often lacks systematic parameter variations and validations. NEW METHOD: We present a method to systematically tune and validate algorithm parameters in automatic spindle detection algorithms using a moderate number of human raters. RESULTS: Comparing a Hilbert transform-based algorithm to a ground truth constructed by six human raters, this method produced a parameter set yielding an F1 score of 0.82 at 10 ms resolution. The algorithm performance fell within the range of human agreement with the ground truth. Both human and algorithm failures arose largely from disagreement in spindle boundaries rather than spindle occurrence. With no additional tuning, the algorithm performed similarly in recordings from different days or rats. COMPARISON WITH EXISTING METHODS: Most spindle detection algorithms do not perform systematic parameter variations and validation using a ground truth. To our knowledge, our study is the first in which rodent spindle data is scored by humans, and in which an automatic spindle detection algorithm is evaluated with respect to this ground truth. The rodent data from this study make it possible to compare our algorithm with others previously tested on human data. CONCLUSIONS: We present a general ground truth based approach for the tuning and validation of spindle extraction algorithms and suggest that algorithms aimed at extracting precise spindle timing in rats should use a systematic approach for parameter tuning.

VGLUT2 expression in primary afferent neurons is essential for normal acute pain and injury-induced heat hypersensitivity.

Dorsal root ganglia (DRG) neurons, including the nociceptors that detect painful thermal, mechanical, and chemical stimuli, transmit information to spinal cord neurons via glutamatergic and peptidergic neurotransmitters. However, the specific contribution of glutamate to pain generated by distinct sensory modalities or injuries is not known. Here we generated mice in which the vesicular glutamate transporter 2 (VGLUT2) is ablated selectively from DRG neurons. We report that conditional knockout (cKO) of the Slc17a6 gene encoding VGLUT2 from the great majority of nociceptors profoundly decreased VGLUT2 mRNA and protein in these neurons, and reduced firing of lamina I spinal cord neurons in response to noxious heat and mechanical stimulation. In behavioral assays, cKO mice showed decreased responsiveness to acute noxious heat, mechanical, and chemical (capsaicin) stimuli, but responded normally to cold stimulation and in the formalin test. Strikingly, although tissue injury-induced heat hyperalgesia was lost in the cKO mice, mechanical hypersensitivity developed normally. In a model of nerve injury-induced neuropathic pain, the magnitude of heat hypersensitivity was diminished in cKO mice, but both the mechanical allodynia and the microgliosis generated by nerve injury were intact. These findings suggest that VGLUT2 expression in nociceptors is essential for normal perception of acute pain and heat hyperalgesia, and that heat and mechanical hypersensitivity induced by peripheral injury rely on distinct (VGLUT2 dependent and VGLUT2 independent, respectively) primary afferent mechanisms and pathways.