A review of efferent cholinergic synaptic transmission in the vestibular periphery and its functional implications

It has been over 60 years since peripheral efferent vestibular terminals were first identified in mammals, and yet the function of the efferent vestibular system remains obscure. One reason for the lack of progress may be due to our deficient understanding of the peripheral efferent synapse. Although vestibular efferent terminals were identified as cholinergic less than a decade after their anatomical characterization, the cellular mechanisms that underlie the properties of these synapses have had to be inferred. In this review we examine how recent mammalian studies have begun to reveal both nicotinic and muscarinic effects at these terminals and therefore provide a context for fast and slow responses observed in classic electrophysiological studies of the mammalian efferent vestibular system, nearly 40 years ago. Although incomplete, these new results together with those of recent behavioral studies are helping to unravel the mysterious and perplexing action of the efferent vestibular system. Armed with this information, we may finally appreciate the behavioral framework in which the efferent vestibular system operates.

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Endocannabinoid-Mediated Control of Synaptic Transmission

Physiological Reviews ◽

10.1152/physrev.00019.2008 ◽

2009 ◽

Vol 89 (1) ◽

pp. 309-380 ◽

Cited By ~ 824

Author(s):

Masanobu Kano ◽

Takako Ohno-Shosaku ◽

Yuki Hashimotodani ◽

Motokazu Uchigashima ◽

Masahiko Watanabe

Keyword(s):

Synaptic Transmission ◽

Intracellular Signaling ◽

Cannabinoid Receptors ◽

Endocannabinoid System ◽

Brain Regions ◽

New Era ◽

Behavioral Studies ◽

Electrophysiological Studies ◽

The Brain ◽

Subsequent Identification

The discovery of cannabinoid receptors and subsequent identification of their endogenous ligands (endocannabinoids) in early 1990s have greatly accelerated research on cannabinoid actions in the brain. Then, the discovery in 2001 that endocannabinoids mediate retrograde synaptic signaling has opened up a new era for cannabinoid research and also established a new concept how diffusible messengers modulate synaptic efficacy and neural activity. The last 7 years have witnessed remarkable advances in our understanding of the endocannabinoid system. It is now well accepted that endocannabinoids are released from postsynaptic neurons, activate presynaptic cannabinoid CB1 receptors, and cause transient and long-lasting reduction of neurotransmitter release. In this review, we aim to integrate our current understanding of functions of the endocannabinoid system, especially focusing on the control of synaptic transmission in the brain. We summarize recent electrophysiological studies carried out on synapses of various brain regions and discuss how synaptic transmission is regulated by endocannabinoid signaling. Then we refer to recent anatomical studies on subcellular distribution of the molecules involved in endocannabinoid signaling and discuss how these signaling molecules are arranged around synapses. In addition, we make a brief overview of studies on cannabinoid receptors and their intracellular signaling, biochemical studies on endocannabinoid metabolism, and behavioral studies on the roles of the endocannabinoid system in various aspects of neural functions.

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Defining the Role of Attention in Hierarchical Auditory Processing

Audiology Research ◽

10.3390/audiolres11010012 ◽

2021 ◽

Vol 11 (1) ◽

pp. 112-128

Author(s):

Caitlin N. Price ◽

Deborah Moncrieff

Keyword(s):

Auditory Processing ◽

Auditory Pathway ◽

Simultaneous Recording ◽

Neural Encoding ◽

Top Down ◽

Attentional Processes ◽

Clinical Interventions ◽

Speech In Noise ◽

Behavioral Studies ◽

Electrophysiological Studies

Communication in noise is a complex process requiring efficient neural encoding throughout the entire auditory pathway as well as contributions from higher-order cognitive processes (i.e., attention) to extract speech cues for perception. Thus, identifying effective clinical interventions for individuals with speech-in-noise deficits relies on the disentanglement of bottom-up (sensory) and top-down (cognitive) factors to appropriately determine the area of deficit; yet, how attention may interact with early encoding of sensory inputs remains unclear. For decades, attentional theorists have attempted to address this question with cleverly designed behavioral studies, but the neural processes and interactions underlying attention’s role in speech perception remain unresolved. While anatomical and electrophysiological studies have investigated the neurological structures contributing to attentional processes and revealed relevant brain–behavior relationships, recent electrophysiological techniques (i.e., simultaneous recording of brainstem and cortical responses) may provide novel insight regarding the relationship between early sensory processing and top-down attentional influences. In this article, we review relevant theories that guide our present understanding of attentional processes, discuss current electrophysiological evidence of attentional involvement in auditory processing across subcortical and cortical levels, and propose areas for future study that will inform the development of more targeted and effective clinical interventions for individuals with speech-in-noise deficits.

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Human spatial representation: what we cannot learn from the studies of rodent navigation

Journal of Neurophysiology ◽

10.1152/jn.00781.2017 ◽

2018 ◽

Vol 120 (5) ◽

pp. 2453-2465 ◽

Cited By ~ 2

Author(s):

Mintao Zhao

Keyword(s):

Spatial Representation ◽

Spatial Information ◽

Storage System ◽

Neural Mechanisms ◽

Cellular Mechanisms ◽

Human Navigation ◽

Behavioral Studies ◽

Closing The Loop ◽

Species Similarity ◽

Shed Light

Studies of human and rodent navigation often reveal a remarkable cross-species similarity between the cognitive and neural mechanisms of navigation. Such cross-species resemblance often overshadows some critical differences between how humans and nonhuman animals navigate. In this review, I propose that a navigation system requires both a storage system (i.e., representing spatial information) and a positioning system (i.e., sensing spatial information) to operate. I then argue that the way humans represent spatial information is different from that inferred from the cellular activity observed during rodent navigation. Such difference spans the whole hierarchy of spatial representation, from representing the structure of an environment to the representation of subregions of an environment, routes and paths, and the distance and direction relative to a goal location. These cross-species inconsistencies suggest that what we learn from rodent navigation does not always transfer to human navigation. Finally, I argue for closing the loop for the dominant, unidirectional animal-to-human approach in navigation research so that insights from behavioral studies of human navigation may also flow back to shed light on the cellular mechanisms of navigation for both humans and other mammals (i.e., a human-to-animal approach).

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5-HT Prolongs Ventral Root Bursting Via Presynaptic Inhibition of Synaptic Activity During Fictive Locomotion in Lamprey

Journal of Neurophysiology ◽

10.1152/jn.00669.2004 ◽

2005 ◽

Vol 93 (2) ◽

pp. 980-988 ◽

Cited By ~ 34

Author(s):

Eric J. Schwartz ◽

Tatyana Gerachshenko ◽

Simon Alford

Keyword(s):

Synaptic Transmission ◽

Presynaptic Inhibition ◽

Cellular Level ◽

Ventral Horn ◽

Pattern Generation ◽

Ventral Root ◽

Synaptic Activity ◽

Fictive Locomotion ◽

Cellular Mechanisms ◽

Bath Application

Locomotor pattern generation is maintained by integration of the intrinsic properties of spinal central pattern generator (CPG) neurons in conjunction with synaptic activity of the neural network. In the lamprey, the spinal locomotor CPG is modulated by 5-HT. On a cellular level, 5-HT presynaptically inhibits synaptic transmission and postsynaptically inhibits a Ca2+-activated K+ current responsible for the slow afterhyperpolarization (sAHP) that follows action potentials in ventral horn neurons. To understand the contribution of these cellular mechanisms to the modulation of the spinal CPG, we have tested the effect of selective 5-HT analogues against fictive locomotion initiated by bath application of N-methyl-d-aspartate (NMDA). We found that the 5-HT1D agonist, L694-247, dramatically prolongs the frequency of ventral root bursting. Furthermore, we show that L694-247 presynaptically inhibits synaptic transmission without altering postsynaptic Ca2+ -activated K+ currents. We also confirm that 5-HT inhibits synaptic transmission at concentrations that modulate locomotion. To examine the mechanism by which selective presynaptic inhibition modulates the frequency of fictive locomotion, we performed voltage- and current-clamp recordings of CPG neurons during locomotion. Our results show that 5-HT decreases glutamatergic synaptic drive within the locomotor CPG during fictive locomotion. Thus we conclude that presynaptic inhibition of neurotransmitter release contributes to 5-HT–mediated modulation of locomotor activity.

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