Advertisement

Acute, specific transgenic ‘silencing’ of Phox2b-expressing neurons in the caudal nucleus tractus solitarius reduces arterial pressure and respiration at rest and in response to hypercapnia in conscious rats

      The caudal nucleus tractus solitarius (cNTS): 1) receives direct afferent inputs from the peripheral baro- and chemo- receptors; 2) contains neurons directly responsive to CO2 (central chemoreceptors); 3) provides excitatory drive to the neurons in the caudal ventrolateral medulla; 4) is a critical region regulating both baro- and chemo- reflexes, and the set-point of arterial pressure. We hypothesize that transgenic ‘silencing’ of Phox2b-expressing neurons in the cNTS will reduce both respiration and arterial pressure at rest and in response to hypercapnia. We acutely and specifically ‘silenced’ Phox2b-expressing neurons in the cNTS by using a lentiviral vector, PRSx8-AlstR-EGFP-LV, that includes the Drosophila allatostatin receptor under the control of a Phox2b specific promoter (PRSx8). We injected the vector into the cNTS of anesthetized male rats (60–90 g) bilaterally & allowed 3–4 weeks for the AlstR-eGFP expression. We then studied the changes of ventilation, arterial pressure, heart rate, and metabolic rate in air and steady-state 7% CO2 before and after ‘silencing’ Phox2b-expressing neurons in the cNTS by i.c.v. injection of allatostatin (2 mM, 10ul) in conscious rats. Allatostatin-induced ‘silencing’ of transfected cNTS Phox2b-expressing neurons: 1) significantly reduced VE/VO2 at rest in wakefulness (~6%; P<0.05; N=8) and in response to hypercapnia in both wakefulness and NREM sleep (~30% P<0.001); 2) decreased arterial pressure in both air and hypercapnia with significance at 7%CO2 in wakefulness (~7%, P<0.05; N=5). We conclude that Phox2b-expressing neurons in the cNTS region have ongoing discharge and contribute to both the control of ventilation and arterial pressure at rest and in response to hypercapnia.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Autonomic Neuroscience: Basic and Clinical
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect