Journal of neurophysiology
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To compare the heat responses of mechanically sensitive and mechanically insensitive A-fiber nociceptors, an electrical search technique was used to locate the receptive fields of 156 A-fibers that innervated the hairy skin in the anesthetized monkey (77 A beta-fibers, 79 A delta-fibers). Two-thirds of these afferents were either low-threshold mechanoreceptors (n = 91) or low-threshold cold receptors (n = 11). Nine A beta-fibers and 41 A delta-fibers were cutaneous nociceptors, and four A delta-fibers innervated subcutaneous tissue. ⋯ Fibers with a type II response exhibited a graded response to heat stimuli, marked fatigue to repeated applications of heat stimuli, and adaptation to sustained heat stimuli similar to that seen in C-fiber nociceptors. First pain sensation to heat is served by type II A-fiber nociceptors that are mechanically insensitive. Type I A-fiber nociceptors likely signal pain to long-duration heat stimuli and may signal first pain sensation to mechanical stimuli.
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Positron emission tomography studies have provided evidence for the involvement of the thalamus and cortex in pain and temperature perception. However, the involvement of these structures in pain and temperature perception of individual subjects has not been studied in detail with high spatial resolution imaging. As a first step toward this goal, we have used functional magnetic resonance imaging (fMRI) to locate discrete regions of the thalamus, insula, and second somatosensory cortex (S2) modulated during innocuous and noxious thermal stimulation. ⋯ Therefore, we provide support for a role of the anterior insula, S2, and thalamus in the perception of pain; whereas the posterior insula appears to be involved in tactile and innocuous temperature perception. These data demonstrate the feasibility of using fMRI for studies of pain, temperature, and mechanical stimuli in individual subjects, even in small regions such as thalamic nuclei. However, the intersubject variability should be considered in future single subject imaging studies and studies that rely on averaged group responses.
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In the previous paper we have demonstrated, by means of field potential and extracellular unit recordings, that bicuculline-induced seizures, which include spike-wave (SW) or polyspike-wave (PSW) complexes, are initiated intracortically and survive ipsilateral thalamectomy. Here, we used multisite field potential and extracellular recordings to validate the patterns of cortical SW/PSW seizures in chronically implanted, behaving cats. To investigate the cellular patterns and excitability during spontaneously occurring and electrically elicited cortical seizures, we used single and dual intracellular recordings from regular-spiking (RS) and fast-rhythmic-bursting (FRB) cortical neurons, in conjunction with field potential recordings from neocortex and related thalamic nuclei, in cats maintained under ketamine-xylazine anesthesia. 1) Invariably, the spontaneous or electrically induced seizures were initiated within the cortex of both behaving and anesthetized animals. ⋯ The FRB neurons fired many more action potentials than RS cells during SW/PSW complexes. Averaged activities triggered by the spiky field potentials or by the steepest slope of depolarization in cortical neurons demonstrated similar relations between intracellular activities and field potentials during sleep and seizure epochs, the latter-being an exaggeration of the depolarizing and hyperpolarizing components of the slow sleep oscillation. 3) During the fast runs, RS cells were tonically depolarized and discharged single action potentials or spike doublets (usually with pronounced spike inactivation), whereas FRB cells discharged rhythmic spike bursts, time locked with the depth-negative field potentials. 4) Neuronal excitability, tested by depolarizing current pulses applied throughout the seizures and compared with pre- and postseizure epochs, showed a decreased number of evoked action potentials during both seizure components (SW/PSW complexes and fast runs), eventually leading to null responses during the postictal depression. 5) Data suggest that interconnected FRB neurons may play an important role in the initiation of cortical seizures. We discuss the similarities between the electrographic patterns described in this study and those found in different forms of clinical seizures.
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In the preceding papers of this series, we have analyzed the cellular patterns and synchronization of neocortical seizures occurring spontaneously or induced by electrical stimulation or cortical infusion of bicuculline under a variety of experimental conditions, including natural states of vigilance in behaving animals and acute preparations under different anesthetics. The seizures consisted of two distinct components: spike-wave (SW) or polyspike-wave (PSW) at 2-3 Hz and fast runs at 10-15 Hz. Because the thalamus is an input source and target of cortical neurons, we investigated here the seizure behavior of thalamic reticular (RE) and thalamocortical (TC) neurons, two major cellular classes that have often been implicated in the generation of paroxysmal episodes. ⋯ To further test this hypothesis, we performed experiments on completely isolated cortical slabs from suprasylvian areas 5 or 7 and demonstrated that electrical stimulation within the slab induces seizures with fast runs and SW/PSW complexes, virtually identical to those elicited in intact-brain animals. The conclusion of all papers in this series is that complex seizure patterns, resembling those described at the electroencephalogram level in different forms of clinical seizures with SW/PSW complexes and, particularly, in the Lennox-Gastaut syndrome of humans, are generated in neocortex. Thalamic neurons reflect cortical events as a function of membrane potential in RE/TC cells and degree of synchronization in cortical neuronal networks.
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Many theories of cerebellar motor learning propose that complex spikes (CS) provide essential error signals for learning and modulate parallel fiber inputs that generate simple spikes (SS). These theories, however, do not satisfactorily specify what modality is represented by CS or how information is conveyed by the ultra-low CS firing rate (1 Hz). To further examine the function of CS and the relationship between CS and SS in the cerebellum, CS and SS were recorded in the ventral paraflocculus (VPFL) of awake monkeys during ocular following responses (OFR). ⋯ A cross-correlation analysis of SS that are triggered by CS revealed that short-term modulation, that is, the brief pause in SS caused by CS, does not account for the reciprocal modulation of SS and CS. The results also showed that three major aspects of the CS and SS individual cell firing characteristics were negatively correlated on a cell-to-cell basis: the preferred direction of stimulus motion, the mean percent change in firing rate induced by upward stimulus motion, and patterns of temporal firing probability. These results suggest that CS may contribute to long-term interactions between parallel and climbing fiber inputs, such as long-term depression and/or potentiation.