Activity-dependent plasticity in the isolated embryonic avian brainstem following manipulations of rhythmic spontaneous neural activity

Abstract

When rhythmic spontaneous neural activity (rSNA) first appears in the embryonic chick brainstem and cranial nerve motor axons it is principally driven by nicotinic neurotransmission (NT). At this early age, the nicotinic acetylcholine receptor (nAChR) agonist nicotine is known to critically disrupt rSNA at low concentrations (0.1–0.5 µM), which are levels that mimic the blood plasma levels of a fetus following maternal cigarette smoking. Thus, we quantified the effect of persistent exposure to exogenous nicotine on rSNA using an in vitro developmental model. We found that rSNA was eliminated by continuous bath application of exogenous nicotine, but rSNA recovered activity within 6–12 h despite the persistent activation and desensitization of nAChRs. During the recovery period rSNA was critically driven by chloride-mediated membrane depolarization instead of nicotinic NT. To test whether this observed compensation was unique to the antagonism of nicotinic NT or whether the loss of spiking behavior also played a role, we eliminated rSNA by lowering overall excitatory drive with a low [K+]o superfusate. In this context, rSNA again recovered, although the recovery time was much quicker, and exhibited a lower frequency, higher duration, and an increase in the number of bursts per episode when compared to control embryos. Importantly, we show that the main compensatory response to lower overall excitatory drive, similar to nicotinergic block, is a result of potentiated chloride mediated membrane depolarization. These results support increasing evidence that early neural circuits sense spiking behavior to maintain primordial bioelectric rhythms. Understanding the nature of developmental plasticity in the nervous system, especially versions that preserve rhythmic behaviors following clinically meaningful environmental stimuli, both normal and pathological, will require similar studies to determine the consequences of feedback compensation at more mature chronological ages.

Motor inactivity in hibernating frogs: Linking plasticity that stabilizes neuronal function to behavior in the natural environment

“…However, jump performance in frogs is reduced after hibernation (Renaud & Stevens, ), implying that a cold body temperature does not mean that all motor systems will necessarily retain the capacity for normal function throughout the winter. In addition, recent work in the respiratory control system of birds and rodents shows that rhythm generating networks and motoneurons exhibit compensation in response to activity challenges (Braegelmann, Streeter, Fields, & Baker, ; Mahamed, Strey, Mitchell, & Baker‐Herman, ; Vincen‐Brown, Revill, & Pilarski, ). These data suggested that the hibernation environment may trigger homeostatic forms of plasticity that are integrated to help frogs breathe adequately after inactivity.…”

Compensatory changes in GABAergic inhibition are differentially expressed in the respiratory network to promote function following hibernation

“…On the other hand, feedback mechanisms appear to protect the drive to breath by stabilizing motor output in response to environmental perturbations. Along these lines, respiratory motor inactivity in different vertebrate species triggers plasticity that can compensate for this disturbance to restore respiratory activity (Streeter and Baker-Herman, 2014;Brown et al, 2016;Santin, 2019). To date, most mechanistic work has focused on excitatory synapses of motoneurons as targets of such plasticity; however, alterations in fast synaptic inhibition are often triggered by changes in neuronal activity in a variety of different neural systems (Benevento et al, 1995;Hendry et al, 1994;Hendry & Jones, 1986, 1988Rutherford et al, 1997;Hartman et al, 2006;Kilman et al, 2002).…”