Cooperative Glutamatergic and Cholinergic Mechanisms Generate Short-Term Modifications of Synaptic Effectiveness in Prepositus Hypoglossi Neurons

Abstract

To maintain horizontal eye position on a visual target after a saccade, extraocular motoneurons need a persistent (tonic) neural activity, called "eye-position signal," generated by prepositus hypoglossi (PH) neurons. We have shown previously in vitro and in vivo that this neural activity depends, among others mechanisms, on the interplay of glutamatergic transmission and cholinergic synaptically triggered depolarization. Here, we used rat sagittal brainstem slices, including PH nucleus and paramedian pontine reticular formation (PPRF). We made intracellular recordings of PH neurons and studied their synaptic activation from PPRF neurons. Train stimulation of the PPRF area evoked a cholinergic-sustained depolarization of PH neurons that outlasted the stimulus. EPSPs evoked in PH neurons by single pulses applied to the PPRF presented a short-term potentiation (STP) after train stimulation. APV (an NMDA-receptor blocker) or chelerythrine (a protein kinase-C inhibitor) had no effect on the sustained depolarization, but they did block the evoked STP, whereas pirenzepine (an M 1 muscarinic antagonist) blocked both the sustained depolarization and the STP of PH neurons. Thus, electrical stimulation of the PPRF area activates both glutamatergic and cholinergic axons terminating in the PH nucleus, the latter producing a sustained depolarization probably involved in the genesis of the persistent neural activity required for eye fixation. M 1 -receptor activation seems to evoke a STP of PH neurons via NMDA receptors. Such STP could be needed for the stabilization of the neural network involved in the generation of position signals necessary for eye fixation after a saccade.

Dysregulation of Phospholipid Metabolism in Synaptic Membranes and Their Role in Encephalopathy Forming After a Hemorrhagic Shock

“…Thus, the initial reduction of PI level in the synaptic membranes of the frontal part of the brain and the medulla oblongata during the initial stage of HS [7,8] may be associated with an increased secretion of neurotransmitters -noradrenaline and acetylcholine, -induced by blood loss and may be reflexion of the existence of the of critical cellular mechanisms which control the modulation of the excitability of neurons and are ways to maintenance of their viability. Moreover, adrenergic and cholinergic hyperactivity of the CNS can be considered as one of the mechanisms of receptors stimulation of EAAs, what is consistent with the existing ideas about the significance in the regulation of these receptors work of adrenergic and cholinergic influences [34,35]. The activation of metabotropic glutamate receptors, apparently, significantly contributes to enhancing compensatory mechanisms of neurotransmission.…”

Anatomical and pharmacological relationship between acetylcholine and nitric oxide in the prepositus hypoglossi nucleus of the cat: Functional implications for eye‐movement control

“…These spontaneous and vestibularly induced eye movements induced by carbachol administration are qualitatively similar to those observed after NOS I-inhibitor injections (Moreno-López et al, 1996, and to those induced by microinjection of GABAergic and glycinergic receptor antagonists in the PH nucleus (Moreno-López et al, 2002), suggesting that a velocity imbalance is the exclusive effect induced by the unilateral depolarization of the PH nucleus. Moreover, the depolarizing effect of carbachol in the PH nucleus is supported by in vitro studies in the PH nucleus of rat, where intracellularly recorded neurons were depolarized with carbachol and inhibited with atropine (Navarro-López et al, 2004, 2005.…”

“…The concept of oculomotor integrator presupposes that velocity signals must be mathematically integrated to generate a proportional eyeposition signal (Robinson, 1975). In previous works it was shown that cholinoceptive neurons in the PH nucleus produce a persistent tonic activity (Navarro-López et al, 2004, 2005 that could be proportional to the amount of ACh received, providing ABD motoneurons with a tonic signal. Thus, to produce a correct eye-position signal, cholinoceptive neurons must receive an amount of ACh proportional to the net eye-velocity command.…”

“…Recently, Navarro-López et al (2005) have shown in PH neurons of rats that activation of muscarinic M 1 receptors enhances synaptic currents mediated by NMDA receptors via protein kinase C, suggesting that this short-term potentiation could play an important role in the stabilization of the neural network. In parallel, an NO signaling cascade has been demonstrated to induce long-term potentiation in Purkinje cells (Smith and Otis, 2003), hippocampus (Hawkins et al, 1998), and cerebral cortex (Centonze et al, 1999).…”

Gaze shift duration, independent of amplitude, influences the number of spikes in the burst for medium-lead burst neurons in pontine reticular formation

“…It may not be realistic, however, to assume that real neurons would behave in this way. For example, it has been suggested that neural integration is a result of synaptic effects, such as short-term potentiation, that enhance the excitability of the postsynaptic cell as a function of the number of input spikes (Navarro-López et al 2004, 2005; Shen 1989). Navarro-López et al (2004) recorded intracellularly from nucleus prepositus hypoglossi (NPH) neurons and reported a sustained depolarization of the membrane potential in response to stimulation of PPRF.…”