Figure 11. Working model of the sympathetic chemoreflexes.

A, peripheral chemoreflex. The increased SND is mediated primarily by activation of the bulbospinal sympathoexcitatory neurons of the RVLM. The excitatory drive of RVLM neurons operates via a direct glutamatergic input from commNTS neurons and via a di-synaptic input that relays via the intrinsically chemosensitive neurons of RTN. The latter pathway is therefore modulated by the degree of central chemoreceptor stimulation. The respiratory modulation of SND and RVLM neurons is seen as deriving from two mechanisms, respiratory-phasic activation by the CPG (respiratory rhythm and pattern-generating network, in blue) of the GABAergic neurons that mediate the sympathetic baroreflex (neuron in red) and respiratory-phasic inhibition of RTN neurons (red arrow, transmitter unidentified). The first mechanism causes an active inhibition of RVLM neurons and the second causes a disfacilitation of RVLM neurons via reduction in RTN discharges. In combination, these two processes attenuate the activation of RVLM neurons during chemoreceptor stimulation and cause the respiratory modulation of SND. B, central chemoreflex. The increased SND caused by raising CNS P_CO2 is driven via activation of the bulbospinal sympathoexcitatory neurons of the RVLM. The relevant chemoreceptors are located in the RVLM region. The activation of RVLM neurons by extracellular fluid acidification is mediated synaptically via the chemosensitive neurons of RTN and, possibly, by the intrinsic chemosensitivity of the RVLM sympathoexcitatory neurons. The respiratory modulation of RVLM neurons and SND has the same mechanism as in the case of the peripheral chemoreflex (CPG-mediated activation of the CVLM neurons and CPG-mediated inhibition of the RTN). CNS acidification activates the CPG via chemoreceptors located in the RTN and/or the rVRG-pre-Bötzinger region but not in the NTS. The integrative properties of the CVLM GABAergic neurons that relay the sympathetic baroreflex (in red) account for the well-documented potentiation of the baroreflex caused by increasing CPG activity. The scheme only applies to the effect of chemoreceptors on the baroregulated sympathetic efferents that control the heart and resistance vessels. The scheme is not applicable to other sympathetic efferents (e.g. to skin or brown adipose fat). Excitatory neurons in green (large circles, cell bodies; small circles, ionotropic glutamatergic synapses; green arrows, neurochemically uncharacterized excitatory connections). In red, GABAergic CVLM neurons involved in the sympathetic baroreflex. Red arrow, neurochemically unidentified inhibitory input from the CPG to RTN neurons. CPG, central pattern generator; CVLM, caudal ventrolateral medulla; LRN, lateral reticular nucleus; RTN, retrotrapezoid nucleus; RVLM, rostral ventrolateral nucleus; for other abbreviations see Fig. 2.