NMDA and GABA_Areceptors in the rat Kölliker‐Fuse area control cardiorespiratory responses evoked by trigeminal ethmoidal nerve stimulation

Abstract

1. Electrical stimulation (10 s) of the ethmoidal nerve (EN5) evokes the nasotrigeminal reflex responses, including apnoea, bradycardia and rise in arterial blood pressure. In the present study, we examined the involvement of N-methyl-ª_aspartate (NMDA), AMPAÏkainate, (ã_aminobutyric acidA (GABAA) and glycine receptors in the K olliker-Fuse (KF) nucleus in the mediation of the nasotrigeminal reflex responses. 2. Unilateral injections (n = 6) of 50-100 nl of the NMDA receptor antagonist AP5 into the KF area led to a significant blockade of the EN5-evoked respiratory depression and bradycardia. Injections placed into the midlevel of the KF area were most effective (80-90% blockade). The rise in arterial blood pressure remained unaffected. 3. Unilateral injections (n = 6) of the AMPAÏkainate receptor antagonist CNQX into the KF area failed to block EN5-evoked autonomic responses significantly. 4. Unilateral injections (n = 5) of the GABAA receptor antagonist bicuculline enhanced the EN5-evoked respiratory depression and bradycardia. The effect persisted for up to 30 s after stimulation. Bicuculline injections into the midlevel of the KF area were most effective. The increase in arterial blood pressure remained unaffected. 5. Unilateral injections (n = 5) of the glycine receptor antagonist strychnine into the KF area did not produce any significant effects on EN5-evoked autonomic responses. 6. Our results suggest that the KF area represents a mandatory relay for the nasotrigeminally induced apnoea and bradycardia which are predominantly mediated by NMDA receptors in the KF. Furthermore, it appears that KF neurons are under a potent GABAergic inhibitory control. The EN5-evoked rise in arterial blood pressure was not altered by any of the drugs and, therefore, appears not to be mediated via the KF.

The Kölliker-Fuse nucleus: a review of animal studies and the implications for cranial nerve function in humans

“…A total of 20 studies were identified that reported a relationship between KF and cranial nerve function, and these involved the trigeminal (6 studies) [14][15][16][17][18][19], vagus (9) [4,[20][21][22][23][24][25][26][27] and hypoglossal (5) [28][29][30][31][32] nerves. The experimental techniques used in obtaining these findings are summarized in Table 1.…”

GABA, GABA transporters, GABAAreceptor subunits, and GAD mRNAs in the rat parabrachial and K�lliker-Fuse nuclei

“…Recently, we demonstrated that the KF is a mandatory relay site for the mediation of trigeminally evoked apnea and bradycardia, which represent the hallmarks of the diving response Herbert, 1996, 1997). Injections of the GABA A receptor antagonist bicuculline into the KF prior to trigeminal ethmoidal nerve stimulation led to a strong enhancement of the reflex responses (Dutschmann and Herbert, 1998), suggesting that KF neurons are under a potent GABAergic inhibition. Lack of this GABAergic inhibition in the KF might be important with respect to life-threatening phenomena such as the sudden infant death syndrome.…”

Pontine respiratory activity involved in inspiratory/expiratory phase transition

“…At the same time, it has been demonstrated that chemical or electrical stimulation of the medial parabrachial complex (mPB) or Kö lliker -Fuse nucleus (KF) can evoke phase resetting and IOS in vagi intact animals (Oku & Dick 1992;Chamberlin & Saper 1994, 1998Dutschmann & Herbert 1998, 2006Okazaki et al 2002). However, these pontinemediated responses were attributed to various protective reflex behaviours (Dutschmann et al 2004) and were not interpreted as a critical contribution of the pons to IOS and IE phase transition during normal breathing.…”