Journal of neurophysiology
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The cellular proteins that underlie mechanosensation remain largely enigmatic in mammalian systems. Mechanically sensitive ion channels are thought to distinguish pressure, stretch, and other types of tactile signals in skin. Transient receptor potential canonical 1 (TRPC1) is a candidate mechanically sensitive channel that is expressed in primary afferent sensory neurons. ⋯ Additionally, we used repeated light, presumably innocuous punctate stimuli with a low threshold von Frey filament (0.68 mN). In agreement with our electrophysiological data in light-touch afferents, TRPC1-deficient mice exhibited nearly a 50% decrease in behavioral responses to both the light-stroke and light punctate mechanical assays when compared with wild-type controls. In contrast, TRPC1-deficient mice exhibited normal paw withdrawal response to more intense mechanical stimuli that are typically considered measures of nociceptive behavior.
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Paired-pulse transcranial magnetic stimulation (ppTMS) is a safe and noninvasive tool for measuring cortical inhibition in humans, particularly in patients with disorders of cortical inhibition such as epilepsy. However, ppTMS protocols in rodent disease models, where mechanistic insight into the ppTMS physiology and into disease processes may be obtained, have been limited due to the requirement for anesthesia and needle electromyography. To eliminate the confounding factor of anesthesia and to approximate human ppTMS protocols in awake rats, we adapted the mechanomyogram (MMG) method to investigate the ppTMS inhibitory phenomenon in awake rats and then applied differential pharmacology to test the hypothesis that long-interval cortical inhibition is mediated by the GABA(A) receptor. ⋯ With pharmacological testing, time course observations showed that ppTMS-MMG inhibition was acutely reduced following PTZ (P < 0.05), acutely enhanced after PB (P < 0.01) injection, and then recovered to pretreatment baseline after 1 h. Our data support the application of the ppTMS-MMG technique for measuring the cortical excitability in awake rats and provide the evidence that GABA(A) receptor contributes to long-interval paired-pulse cortical inhibition. Thus ppTMS-MMG appears a well-tolerated biomarker for measuring GABA(A)-mediated cortical inhibition in rats.
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The amygdala plays a central role in evaluating the significance of acoustic signals and coordinating the appropriate behavioral responses. To understand how amygdalar responses modulate auditory processing and drive emotional expression, we assessed how neurons respond to and encode information that is carried within complex acoustic stimuli. We characterized responses of single neurons in the lateral nucleus of the amygdala to social vocalizations and synthetic acoustic stimuli in awake big brown bats. ⋯ In most neurons, variation in response duration depended, in part, on persistent excitatory discharge that extended beyond stimulus duration. Information in persistent firing duration was significantly greater than in spike rate, and the majority of neurons displayed more information in persistent firing, which was more likely to be observed in response to aggressive vocalizations (64%) than appeasement vocalizations (25%), suggesting that persistent firing may relate to the behavioral context of vocalizations. These findings suggest that the amygdala uses a novel coding strategy for discriminating among vocalizations and underscore the importance of persistent firing in the general functioning of the amygdala.
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The rostral ventromedial medulla (RVM) is part of descending circuitry that modulates nociceptive processing at the level of the spinal cord. RVM output can facilitate pain transmission under certain conditions such as inflammation, and thereby contribute to hyperalgesia. Evidence suggests that substance P and activation of neurokinin-1 (NK-1) receptors in the RVM are involved in descending facilitation of nociception. ⋯ After capsaicin injection, excitatory responses of ON cells and inhibitory responses of OFF cells evoked by mechanical and heat stimuli applied to the injected, but not contralateral, paw were increased. Injection of the NK-1 antagonist L-733,060 did not alter evoked responses of ON or OFF cells but attenuated the capsaicin-evoked enhanced responses of ON cells to mechanical and heat stimuli with less of an effect on the enhanced inhibitory responses of OFF cells. These data support the notion that descending facilitation from RVM contributes to hyperalgesia and that NK-1 receptors, presumably located on ON cells, play an important role in initiating descending facilitation of nociceptive transmission.
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Auditory cortical processing is thought to be accomplished along two processing streams. The existence of a posterior/dorsal stream dealing, among others, with the processing of spatial aspects of sound has been corroborated by numerous studies in several species. An anterior/ventral stream for the processing of nonspatial sound qualities, including the identification of sounds such as species-specific vocalizations, has also received much support. ⋯ Our study demonstrates that specialization for sound-identity processing can be found very early in the auditory ventral stream. Furthermore, the fact that this processing develops over time can shed light on underlying mechanisms. Finally, we show that population analysis is a more sensitive method for revealing functional specialization than conventional types of analysis.