Adenosine A1 receptors are involved in the modulation of the rhythmical respiration in neonatal rat brainstem slice in vitro.

This study was designed to investigate whether adenosine A1 receptors could modulate primary rhythmical respiration in mammals. Experiments were performed in in vitro brainstem slice preparations from neonatal rats. These preparations included the medial region of the nucleus retrofacialis (mNRF) with the hypoglossal nerve rootlets retained. The activity of the inspiration-related neurons (I neurons) in mNRF and respiratory rhythmical discharge activity (RRDA) of the hypoglossal nerve rootlets were simultaneously recorded by using microelectrodes and suction electrodes, respectively. Possible roles of adenosine A1 receptors in rhythmical respiration were investigated by administration of adenosine A1 receptor agonist R-phenylisopropyl-adenosine (R-PIA) and its specific antagonist 8-cyclopentyl-1,3- dipropylxanthine (DPCPX) into a modified Kreb's perfusion solution (MKS). DPCPX induced a significant decrease in the expiratory time and the respiratory cycles, and an increase in the discharge frequency and peak frequency of I neurons in the middle phase of inspiration. However, R-PIA significantly decreased the inspiratory time and integral amplitude as well as prolonged respiratory cycle. Moreover, the discharge frequency and the peak frequency of I neurons were decreased in the middle phase of inspiration, but not in the initial and terminal phases. The effect of R-PIA on rhythmical discharges could be partially reversed by additional application of DPCPX. These results indicate that adenosine A1-receptors are possibly involved in the modulation of rhythmical respiration through the inhibitory synaptic input from I neurons.

[Nitric oxide is involved in the modulation of central respiratory rhythm].

This experiment was expected to test whether nitric oxide (NO) exerted significant effect on the central respiratory rhythm. Experiments were performed on in vitro brainstem slice preparations from neonatal rats. These preparations include the medial region of the nucleus retrofacialis (mNRF); a part of pre-Bötinger complex, ventral respiratory group (VRG) and dorsal respiratory group (DRG). Respiratory-related burst activities were recorded from hypoglossal nerve rootlets before and during superfusion of the slice preparation with L-Arginine (L-Arg), sodium nitroprusside (SNP) or 7-nitro indazole (7-NI, an inhibitor of NO synthase). After perfusion with L-Arg and SNP, there was no significant change in respiratory rhythmical discharge activity (RRDA), but 7-NI decreased the integral amplitude of burst and inspiratory time. These results indicate that NO may take part in the inspiratory off-switching mechanism and that it also modulates the amplitude of respiratory-related bursts.

Projections between the medial region of the nucleus retrofacialis and other respiratory regions in rats brainstem.

OBJECTIVE: To study the projections between the medial region of the nucleus retrofacialis (mNRF) and other respiratory regions in rat brainstem. METHODS: Twenty-five adult SD rats were used in this study, which received anesthesia with sodium pentobarbitone. Retrograde/anterograde tracing methods were employed by unilateral microinjection into mNRF with 30% horseradish peroxidase (HRP, 0.5-1.0 microliter1) in 13 rats. Another 5 rats with injections of HRP and 2 with WGA-HRP into the regions 2 mm off mNRF served as control groups. and with 5% wheat germ agglutinin-conjugated HRP (WGA-HRP, 20-60 nl) in 5 rats (with another 2 receiving the injections as control). RESULTS: It was found that HRP-labeled neuronal somas and WGA-HRP labeled terminal fibers were found in many respiration-related regions in rat brainstem such as the nucleus tractus solitarius, nucleus ambiguous, gigantocellular reticular nucleus and so forth. CONCLUSIONS: There are comprehensive projections between mNRF and other respiratory regions in rat brainstem, and these respiratory regions may be involved in basic respiratory rhythm regulation via these connections with mNRF.

Corticothalamic synchronization leads to c-fos expression in the auditory thalamus.

In this study, we investigated the relationship between c-fos expression in the auditory thalamus and corticofugal activation. The contribution of neurotransmitters and related receptors, the involvement of thalamic reticular nucleus (TRN), and the role of neuronal firing patterns in this process were also examined. The principal nuclei of the medial geniculate body (MGB) showed c-fos expression when the auditory cortex (AC) was activated by direct injection of bicuculline methobromide. However, no expression was detectable with acoustic stimuli alone. This indicated that c-fos expression in the principal nuclei of the MGB was triggered by the corticofugal projection. c-fos expression could be elicited in the MGB by direct injection of glutamate. Direct administration of acetylcholine, alternatively, had no effect. Bicuculline methobromide injection in the AC also triggered synchronized oscillatory activities sequentially in the AC and MGB. Cortically induced c-fos expression in the MGB was not mediated by a pathway involving the TRN because it remained intact after a TRN lesion with kainic acid. The present results also conclude that c-fos expression is not simply associated with firing rate, but also with neuronal firing pattern. Burst firings that are synchronized with the cortical oscillations are proposed to lead to c-fos expression in the principal nuclei of the MGB.