Induction of long-lasting depolarization in medioventral medulla neurons by cholinergic input from the pedunculopontine nucleus

Abstract

Stimulation of the pedunculopontine nucleus (PPN) is known to induce changes in arousal and postural/locomotor states by activation of such descending targets as the caudal pons and the medioventral medulla (MED). Previously, PPN stimulation was reported to induce prolonged responses (PRs) in intracellularly recorded caudal pontine neurons in vitro. The present study used intracellular recordings in semihorizontal slices from rat brain stem (postnatal days 12-21) to determine responses in MED neurons following PPN stimulation. One-half (40/81) of MED neurons showed PRs after PPN stimulation. MED neurons with PRs had shorter duration action potential, longer duration afterhyperpolarization, and higher amplitude afterhyperpolarization than non-PR MED neurons. PR MED neurons were significantly larger (568 +/- 44 microm2) than non-PR MED neurons (387 +/- 32 microm2). The longest mean duration PRs and maximal firing rates during PRs were induced by PPN stimulation at 60 Hz compared with 10, 30, or 90 Hz. The muscarinic cholinergic agonist carbachol induced depolarization in all PR neurons tested, and the muscarinic cholinergic antagonist scopolamine reduced or blocked carbachol- and PPN stimulation-induced PRs in all MED neurons tested. These findings suggest that PPN stimulation-induced PRs may be due to activation of muscarinic receptor-sensitive channels, allowing MED neurons to respond to a transient, frequency-dependent depolarization with long-lasting stable states. PPN stimulation appears to induce PRs in large MED neurons using parameters known best to induce locomotion.

Cell-Type-Specific Control of Brainstem Locomotor Circuits by Basal Ganglia

“…This population has previously been hypothesized to control locomotion (Skinner et al, 1990). PPTg cholinergic neurons send projections to the ventromedial medulla, depolarizing glutamatergic cells that in turn project to reticulospinal neurons (Brudzynski et al, 1988; Mamiya et al, 2005; Smetana et al, 2010). However other work has shown that these neurons play a major role in gating brain state as part of the ascending reticular activating system (Mena-Segovia et al, 2008; Van Dort et al, 2015).…”

A parallel cholinergic brainstem pathway for enhancing locomotor drive

“…Cholinergic inputs are also believed to activate brainstem neurones in mammals16,33. A group of muscarinoceptive neurons was recently described in mammals in the ventromedial medulla close to the pontine border34 at a location similar to that of the muscarinoceptive cells in lampreys. These cells receive cholinergic inputs from the pedunculopontine nucleus, known to be part of the mammalian MLR16.…”

Local and Relayed Effects of Deep Brain Stimulation of the Pedunculopontine Nucleus

“…Application of electrical or chemical, in particular, cholinergic agonists, to the pontomedullary region will induce decreases in muscle tone at some sites but at other sites elicit locomotor movements [12,53]. Specifically, descending PPN projections to large reticulospinal neurons (presumably involved in the atonia of REM sleep) induce long duration hyperpolarization; however, PPN projections to medium size interneurons induce depolarization that drives spinal locomotor pattern generators [54,55]. High frequency stimulation (>100 Hz) was effective in eliciting this inhibition.…”

“…High frequency stimulation (>100 Hz) was effective in eliciting this inhibition. Therefore, on the one hand, the PPN inhibits large neurons that drive extensor muscle tone and standing, while, on the other hand, it depolarizes medium-sized neurons that drive locomotion, thus creating push–pull reciprocity between postural drive and locomotor drive [55]. Issue 8.…”