Respiratory modulation of neuronal discharge in the central nucleus of the amygdala during sleep and waking states
Zhang JX, Harper RM, and Frysinger RC (1986) Respiratory modulation of neuronal discharge in the central nucleus of the amygdala during sleep and waking states. Exp Neurol 91:1 193–207.
Abstract: The relationship between neuronal discharge in the central nucleus of the amygdala (ACE) and timing of the respiratory cycle was assessed during quiet and active sleep and during the waking state. Of 169 neurons recorded from the ACE in intact, drug-free cats, 22% discharged phasically with the respiratory cycle during at least one sleep or waking state. The dependency between neuronal discharge and the respiratory cycle was typically strong in only one state. Forty-three percent of the respiratory-related neurons were most strongly correlated with the respiratory cycle during the waking state (AW). An additional 30% were most strongly related to the respiratory cycle during quiet sleep (QS), whereas only 11% showed the strongest dependency during rapid eye movement (REM) sleep. Half of the ACE neurons (49%) discharged at frequencies less than 10 spikes per second, and the most common trend in firing rate across states was one in which neurons fired more rapidly during AW and REM than during QS. No relationship between discharge rate of ACE neurons in the three states and propensity for phasic discharge with the respiratory cycle could be demonstrated.
- Study in cat of link between respiration and neural activity in amygdala. One-fifth of neurons in amygdalar central nucleus fired in phase with respiration. Waking or phase of sleep influenced the dependence. The link of amygdala activity and respiration may underlie the link suggested between temporal lobe epilepsy and apnea. In a study in patients, Frysinger and Harper, 1989 found that only about 2% of cells in amygdala showed changes in firing activity with a significant relation to the timing of respiration. If >20% of neurons in the central nucleus of the amygdala also show respiration-related activity patterns in humans, the much lower percentage in Frysinger and Harper, 1989 could be due to infrequent recordings from the central nucleus in that study. Removal of all or part of amygdala on one side is often part of epilepsy surgery, so if amygdalar neuron activity influences respiration directly one would predict changes in an individual's respiration after excision. This could be readily tested. In postmortem tissue from 15 cases of SUDEP examination of the amygdala showed neuronal loss in the medial division of the lateral nucleus, but noted that such loss is also found in patients with chronic epilepsy without SUDEP (Thom et al., 1999). Anatomic evidence of a specific strucutural change in SUDEP victims would only be possible if seizures in these individuals are categorically different from those in epilepsy patients who do not have SUDEP, and this has not been shown. Near-SUDEP cases that have occurred during monitoring do not appear to show any fundamental difference, even for what would apparently have been the terminal seizure. Saunders and Rosene 1988 detailed projections from other amygdalar nuclei (lateral and accessory basal) to entorhinal and perirhinal cortex. Efferent projections between amygdala and hippocampus in macaque Saunders et al., 1988 include those from amygdalar accessory basal, medial basal, and cortical nuclei to hippocampus, and from hippocampal CA1' and prosubiculum project to amygdala. Seizure spread to the amygdalar region was shown in a patient to co-occur with apnea, and stimulation of the amygdala was shown in a few patients to cause apnea, which was not accompanied by dyspnea Dlouhy et al., 2015. A study in seven patients found that stimulation of the central nucleus of the amygdala induced apnea which stops if the patient is instructed to inhale and prevented if the patient breathes through the mouth before the stimulation. Another study in patients found that stimulation of the amygdala caused apnea Lacuey et al., 2017. Almost fifty years earlier Respiratory arrest from seizure discharges in the limbic system saw altered respiration with amygdalar (or peri-amygdalar) stimulation in patients, and noted that the resulting hypoxia in one case appeared to alter EEG. Projects from amygdala to brainstem Hopkins and Holstege 1978 presumably underlie the effect.
Amygdalar stimulation elicits a pressor response, and this is also modulated by sleep state Frysinger et al., 1984.