Journal of neurophysiology
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We investigated the afferents and intracortical synaptic organization of the anterior cingulate cortex (ACC) during noxious electrical stimulation. Extracellular field potentials were recorded simultaneously from 16 electrodes spanning all layers of the ACC in male Sprague-Dawley rats anesthetized by halothane inhalation. Laminar-specific transmembrane currents were calculated with the current source density analysis method. ⋯ High-frequency stimulation (100 Hz, 11 pulses) enhanced evoked responses in the ACC and evoked medial thalamic (MT) unit activities. MT lesions blocked evoked responses in the ACC. Our results demonstrated that two distinct synaptic circuits in the ACC were activated by noxious stimuli and that the MT is the major thalamic relay that transmits nociceptive information to the ACC.
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Fluctuations in the amplitude of a sound play an important role in our perception of pitch and acoustic space, but their neural analysis has not been fully elucidated. The ventral nucleus of the lateral lemniscus (VNLL) has been implicated in the processing of such temporal features of a sound. This study examines responses of neurons in the VNLL of unanesthetized rabbits to sinusoidally amplitude modulated tones, a type of stimulus that has often been used to investigate encoding of temporal information. ⋯ The best modulation frequencies of neurons with band-pass rMTFs extended from 14 to 283 Hz. The presence of neurons with band-pass rMTFs in the VNLL suggests that this nucleus plays a role in converting the temporal code for modulation frequency used in lower structures into a rate-based code for use higher in the auditory pathway. The substantial number of neurons with more complex modulation transfer functions indicates that the VNLL has other functions.
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The calmodulin (CaM) inhibitor trifluoperazine (TFP) can produce analgesia when given intrathecally to rats; however, the mechanism is not known. We asked whether TFP could modulate the Na(v)1.7 sodium channel, which is highly expressed in the peripheral nervous system and plays an important role in nociception. We show that 500 nM and 2 muM TFP induce major decreases in Na(v)1.7 and Na(v)1.4 current amplitudes and that 2 muM TFP causes hyperpolarizing shifts in the steady-state inactivation of Na(v)1.7 and Na(v)1.4. ⋯ Rather, our data show that TFP inhibition is state dependent and that the majority of the TFP inhibition depends on specific amino-acid residues in the local anesthetic receptor site in sodium channels. TFP was also effective in vivo in causing motor and sensory blockade after subfascial injection to the rat sciatic nerve. The state-dependent block of Na(v)1.7 channels with nanomolar concentrations of TFP raises the possibility that TFP, or TFP analogues, might be useful for regional anesthesia and pain management and could be more potent than traditional local anesthetics.
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Sphingosine-1-phosphate (S1P) is released by immune cells and is thought to play a key role in chemotaxis and the onset of the inflammatory response. The question remains whether this lipid mediator also contributes to the enhanced sensitivity of nociceptive neurons that is associated with inflammation. Therefore we examined whether S1P alters the excitability of small diameter, capsaicin-sensitive sensory neurons by measuring action potential (AP) firing and two of the membrane currents critical in regulating the properties of the AP. ⋯ In contrast, internal perfusion with GDP-beta-S and S1P increased the number of APs evoked by the current ramp. These results and our finding that the mRNAs for S1PRs are expressed in both the intact dorsal root ganglion and cultures of adult sensory neurons supports the notion that S1P acts on S1PRs linked to G proteins. Together these findings demonstrate that S1P can regulate the excitability of small diameter sensory neurons by acting as an external paracrine-type ligand through activation of G-protein-coupled receptors and thus may contribute to the hypersensitivity during inflammation.
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In monkeys, saccades that repeatedly overshoot their targets adapt to become smaller by the time the monkey has made 1,000-2,000 saccades. In life, adaptation must keep movements accurate for long periods of time. Previous work describes only saccade adaptation that occurs within a few hours. ⋯ In contrast, we could elicit only small additional size reduction after only 1 day of adaptation. A simple model using separate short- and long-term adaptation mechanisms can reproduce many of the features of saccade gain exhibited by monkeys during a 19-day adaptation. We conclude that there is a long-term saccade-adaptation mechanism that is distinct from the well-characterized short-term system and that this newly recognized system is responsible for long-term maintenance of saccade accuracy.