Journal of neurophysiology
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While research on human sensory processing shows that warm input is conveyed from the periphery by specific, unmyelinated primary sensory neurons, its pathways in the central nervous system (CNS) remain unclear. To gain physiological information on the spinal pathways that convey warmth or nociceptive sensations, in 15 healthy subjects, we studied the cerebral evoked responses and reaction times in response to laser stimuli selectively exciting Adelta nociceptors or C warmth receptors at different levels along the spine. To minimize the conduction distance along the primary sensory neuron, we directed CO(2)-laser pulses to the skin overlying the vertebral spinous processes. ⋯ Spinal neurons activated by the warm input had a slower conduction velocity (2.5 m/s) than the nociceptive spinal neurons (11.9 m/s). Brain source analysis of the cerebral responses evoked by the Adelta input yielded a very strong fit for one single generator in the mid portion of the cingulate gyrus; the warmth-related responses were best explained by three generators, one within the cingulate and two in the right and left opercular-insular cortices. Our results support the existence of slow-conducting second-order neurons specific for the sense of warmth.
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Prefrontal cortical dopamine (DA) modulates pyramidal cell excitability directly and indirectly by way of its actions on local circuit GABAergic interneurons. DA modulation of interneuronal functions is implicated in the computational properties of prefrontal networks during cognitive processes and in schizophrenia. Morphologically and electrophysiologically distinct classes of putative GABAergic interneurons are found in layers II-V of rat prefrontal cortex. ⋯ Collectively, these data showed that DA depolarizes FS interneurons by suppressing a voltage-independent 'leak' K(+) current (via D1/D5 receptor mechanism) and an inwardly rectifying K(+) current (via unknown DA mechanisms). Additional suppression of a slowly inactivating K(+) current led to increase in repetitive firing in response to depolarizing inputs. This D1-induced increase in interneuron excitability enhances GABAergic transmission to PFC pyramidal neurons and could represent a mechanism via which DA suppresses persistent firing of pyramidal neurons in vivo.
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Hippocampal CA1 pyramidal cells receive two kinetic classes of GABA(A) receptor-mediated inhibition: slow dendritic inhibitory postsynaptic currents (GABA(A,slow) IPSCs) and fast perisomatic (GABA(A,fast)) IPSCs. These two classes of IPSCs are likely generated by two distinct groups of interneurons, and we have previously shown that the kinetics of the IPSCs have important functional consequences for generating synchronous firing patterns. Here, we studied developmental changes in the properties of GABA(A,fast) and GABA(A,slow) spontaneous, miniature, and evoked IPSCs (sIPSCs, mIPSCs, and eIPSCs, respectively) using whole cell voltage-clamp recordings in brain slices from animals aged P10-P35. ⋯ This effect was observed in animals as young as P13 and was blocked by coapplication of tetrodotoxin, suggesting that NE was acting to increase the spontaneous firing rate of GABA(A,slow) interneurons and consistent with our hypothesis that developmental changes in GABA(A,slow) IPSCs are due to changes in presynaptic excitability. In contrast to the changes we observed in GABA(A,slow) IPSCs, the properties of GABA(A,fast) sIPSCs remained largely constant between P11 and P35, whereas the rate, amplitude, and kinetics of GABA(A,fast) mIPSCs showed significant changes between P10 and P30, suggesting counterbalancing changes in action potential-dependent GABA(A,fast) sIPSCs. These observations suggest differential developmental regulation of the firing properties of GABA(A,fast) and GABA(A,slow) interneurons in CA1 between P10 and P35.
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We have studied the modulatory effects of cholinergic agonists on excitatory postsynaptic currents (EPSCs) in nucleus accumbens (nAcb) neurons during postnatal development. Recordings were obtained in slices from postnatal day 1 (P1) to P27 rats using the whole cell patch-clamp technique. EPSCs were evoked by local electrical stimulation, and all experiments were conducted in the presence of bicuculline methchloride in the bathing medium and with QX-314 in the recording pipette. ⋯ In contrast, CCh produced consistent changes in the membrane and firing properties of medium spiny (MS) neurons when QX-314 was omitted from the recording pipette solution, suggesting that this substance actually blocked postsynaptic cholinergic modulation. Together, these results suggest that ACh can decrease or increase glutamatergic neurotransmission in the nAcb by, respectively, acting on muscarinic and nicotinic receptors located on excitatory terminals. The cholinergic modulation of AMPA/KA and NMDA receptor-mediated neurotransmission in the nAcb during postnatal development could play an important role in activity-dependent developmental processes in refining the excitatory drive on MS neurons by gating specific inputs.
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Nitric oxide (NO) in the paraventricular nucleus (PVN) is involved in the regulation of the excitability of PVN neurons. However, the effect of NO on the inhibitory GABAergic and excitatory glutamatergic inputs to spinally projecting PVN neurons has not been studied specifically. In the present study, we determined the role of the inhibitory GABAergic and excitatory glutamatergic inputs in the inhibitory action of NO on spinally projecting PVN neurons. ⋯ On the other hand, 20 microM bicuculline significantly increased the impulse activity of PVN neurons. In the presence of bicuculline, SNAP or L-arginine both failed to inhibit the firing activity of PVN neurons. This electrophysiological study provides substantial new evidence that NO suppresses the activity of spinally projecting PVN neurons through potentiation of the GABAergic synaptic input.