Journal of neurophysiology
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Nicotine regulates respiratory pattern by modulating excitatory neurotransmission affecting inspiratory neurons within the preBötzinger Complex (preBötC). The nicotinic acetylcholine receptor (nAChR) subtypes mediating these effects are unknown. Using a medullary slice preparation from neonatal rat, we recorded spontaneous respiratory-related rhythm from the hypoglossal nerve (XIIn) and patch-clamped inspiratory neurons in the preBötC simultaneously. ⋯ We do not exclude the possibility that co-assembly of alpha4beta2 with other subunits or other nAChR subtypes are also expressed in preBötC neurons. The parallel changes in the cellular and systems level responses induced by different nicotinic agonists and antagonists support the idea that modulation of excitatory neurotransmission affecting preBötC inspiratory neurons is a mechanism underlying the cholinergic regulation of respiratory pattern (). This study provides a useful model system for evaluating potential therapeutic cholinergic agents for their respiratory effects and side effects.
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Recent discoveries of visceral nociceptive inputs sharing the classical tactile pathway in the dorsal-column medial lemniscus system have opened a new venue for the investigation of somatovisceral interactions. The current study was designed to determine whether somatic innocuous inputs modulate visceral nociceptive transmission at the thalamic level. The investigation was carried out by means of extracellular single-unit recordings in the ventroposterior lateral nucleus of the thalamus in rats anesthetized with pentobarbital. ⋯ Under such circumstances, the original effect of tactile stimulation on CRD responses could be weakened. In conclusion, tactile stimulation may in most circumstances inhibit thalamic neuronal responses to visceral nociceptive input produced by CRD. However, the effect appears to be mild and short-lasting at the individual neuronal level in the VPL thalamus.
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Local perfusion of the dorsal root ganglion (DRG) with tumor necrosis factor alpha (TNF-alpha) in rats induces cutaneous hypersensitivity to mechanical stimuli. Thus we investigated the cellular mechanisms of TNF-alpha-induced mechanical hyperalgesia. The L(4) and L(5) DRGs with the sciatic nerves attached were excised from rats for in vitro dorsal root microfilament recording. ⋯ Acute TNF-alpha application not only evoked discharges in silent fibers, but also enhanced ongoing activity of spontaneously active fibers and increased neuronal sensitivity to electrical stimulation of the peripheral nerves. H-89 (10 microM) and Rp-cAMPS (100 microM) each completely blocked the TNF-alpha-evoked response in most C and Abeta fibers tested but did not affect fiber conductivity. Our results demonstrates that exogenous inflammatory cytokines such as TNF-alpha can elicit a PKA-dependent response in sensory neurons and thus strongly suggest that endogenous TNF-alpha may contribute to the development of certain pathological pain states.
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Although 3alpha-substituted metabolites of progesterone are well established to interact with GABA(A) receptor/Cl(-) channels, the nature of the interaction(s) remains uncertain. We used patch-clamp recording to study the interaction with GABA(A) receptor/Cl(-) channels expressed by embryonic hippocampal neurons differentiating in culture and nonneuronal cells transfected with GABA(A) receptor subunits. Allopregnanolone primarily induced multiphasic current responses in neurons, which were eliminated by bicuculline, an antagonist of GABA at GABA(A) receptor/Cl(-) channels. ⋯ Pertussis toxin treatment eliminated the low-amplitude current and attenuated the high-amplitude current induced by allopregnanolone in a reversible manner. Mastoparan, which activates G proteins directly, triggered a high-amplitude current after a delay, which was blocked by bicuculline. The results indicate that allopregnanolone interacts with GABA(A) receptor/Cl(-) channels expressed by embryonic hippocampal neurons in multiple ways, some of which are mediated by G proteins.
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Comparative Study
Responses of reticulospinal neurons in intact lamprey to pitch tilt.
In the swimming lamprey, a postural control system maintains a definite orientation of the animal's longitudinal axis in relation to the horizon (pitch angle). Operation of this system is based on vestibular reflexes. Important elements of the postural network are the reticulospinal (RS) neurons, which are driven by vestibular input and transmit commands for postural corrections from the brain stem to the spinal cord. ⋯ In addition to the main test (rotation in the pitch plane), the animals were also tested by rotation in the transverse (roll) plane. It was found that 22% of RS neurons responding to pitch tilts also responded to roll tilts. The overlap between the pitch and roll populations suggests that the RS pathways are partly shared by the pitch and roll control systems.