Auditory role of the octavolateral efferent system in a teleost fish

Sensory systems have evolved to provide animals with information about their environments. Information relayed from sensory receptors is processed in the central nervous system to yield a perception of the environment. In the vertebrate auditory system, efferent neurons originate in the brainstem and send projections to the ear, which modify the ascending information before it reaches the brain. The overall role of efferent innervation in sensory perception is poorly understood, and the efferent system remains rather enigmatic. The present studies have examined the anatomy, auditory physiology, and peripheral effects of the efferent neurons in the relatively simple ear of a teleost fish, the sleeper goby (Dormitator latifrons). The anatomy of the auditory nuclei in the brainstem, including the efferent neurons, was studied with retrograde labeling and confocal microscopy. Multiple fluorophore tracers were used to retrogradely label each of the branches of the eighth nerve and lateral line nerves. The auditory physiology of octavolateral efferent neurons was studied using single-cell recording. Efferent neurons responded omnidirectionally to stimuli and had broadly-tuned, low-pass frequency responses. This suggests that they respond generally to the presence and intensity of sounds in the environment, with little directional or frequency selectivity. The effects of efferent activity on the signal-to-noise ratio (SNR) of the auditory system as a whole were studied by stimulating efferent neurons and quantifying the SNR of tone-evoked auditory responses (compound saccular nerve potentials) before and after efferent stimulation. Efferent stimulation decreased the SNR of the responses in quiet conditions, but increased it when tones were masked by broadband noise. This suggests that efferent neurons enhance the encoding of stimuli in difficult listening conditions, where signals are partially masked by noise. These data collectively suggest that the efferent neurons provide a general feedback to the ear, which increases the SNR of the auditory system when noise levels in the environment are high and signals are likely to be masked

Octavolateral projections and organization in the medulla of a teleost fish, the sleeper goby (Dormitator latifrons)

This study is the first to employ simultaneous labeling with different colored fluorescent dyes and confocal microscopy to investigate the central projections of the octavolateral nerves in any fish. Three-dimensional reconstructions of the hindbrain octavolateral nuclei were made and overlap of octavolateral projections was assessed in a teleost, the sleeper goby (Dormitator latifrons). The octavolateral nerves, which innervate the otolithic organs, semicircular canals, and lateral lines, project to seven hindbrain nuclei in diverse, complex patterns. The medulla is generally organized with auditory regions dorsal to vestibular regions. The intermediate subdivision of the descending octaval nucleus (DON) receives interdigitating projections from the otolithic organs, and the dorsomedial DON likely integrates multiple auditory inputs. Afferents from the three otolithic organs (the utricle, saccule, and lagena) project to the intermediate DON in approximately equal proportion, supporting physiological evidence that suggests auditory roles for all three otolithic organs in the sleeper goby. The anterior octaval nucleus receives partially segregated inputs from the octavolateral organs. The dorsal division of the magnocellular octaval nucleus (MgON) receives highly overlapping otolithic organ and semicircular canal input, and we propose that this region is a major octaval integration center. Regions in the ventral medulla (the tangential octaval nucleus, ventral DON, and ventral MgON) receive mainly utricular and semicircular canal inputs, suggesting vestibular roles. Each semicircular canal nerve projects to distinct regions of the hindbrain, with little overlap in most octaval nuclei. Efferent neurons receive bilateral input and project unilaterally to the octavolateral organs

Modulation of auditory signal-to-noise ratios by efferent stimulation

One of the primary challenges that sensory systems face is extracting relevant information from background noise. In the auditory system, the ear receives efferent feedback, which may help it extract signals from noise. Here we directly test the hypothesis that efferent activity increases the signal-to-noise ratio (SNR) of the ear, using the relatively simple teleost ear. Tone-evoked saccular potentials were recorded before and after efferent stimulation, and the SNR of the responses was calculated. In quiet conditions, efferent stimulation suppressed saccular responses to a tone, reducing the SNR. However, when masking noise was added, efferent stimulation increased the SNR of the saccular responses within a range of stimulus combinations. These data demonstrate that auditory efferent feedback can increase SNR in conditions where a signal is masked by noise, thereby enhancing the encoding of signals in noise. Efferent feedback thus performs a fundamental signal processing function, helping the animal to hear sounds in difficult listening conditions

Auditory physiology and anatomy of octavolateral efferent neurons in a teleost fish

Vertebrate hair cell systems receive innervation from efferent neurons in the brain. Here we report the responses of octavolateral efferent neurons that innervate the inner ear and lateral lines in a teleost fish, Dormitator latifrons, to directional linear accelerations, and compare them with the afferent responses from the saccule, the main auditory organ in the inner ear of this species. Efferent neurons responded to acoustic stimuli, but had significantly different response properties than saccular afferents. The efferents produced uniform, omnidirectional responses with no phase-locking. Evoked spike rates increased monotonically with stimulus intensity. Efferents were more broadly tuned and responsive to lower frequencies than saccular afferents, and efferent modulation of the otolithic organs and lateral lines is likely more pronounced at lower frequencies. The efferents had wide dynamic ranges, shallow rate-level function slopes, and low maximum discharge rates. These findings support the role of the efferent innervation of the otolithic organs as part of a general arousal system that modulates overall sensitivity of the peripheral octavolateral organs. In addition, efferent feedback may help unmask biologically relevant directional stimuli, such as those emitted by a predator, prey, or conspecific, by reducing sensitivity of the auditory system to omnidirectional ambient noise

Biogenic amine synthesis and uptake in rodent taste buds

Although adenosine triphosphate (ATP) is known to be an afferent transmitter in the peripheral taste system, serotonin (5-HT) and norepinephrine (NE) have also been proposed as candidate neurotransmitters and have been detected immunocytochemically in mammalian taste cells. To understand the significance of biogenic amines in taste, we evaluated the ability of taste cells to synthesize, transport, and package 5-HT and NE. We show by reverse transcriptase-polymerase chain reaction and immunofluorescence microscopy that the enzymes for 5-HT synthesis, tryptophan hydroxylase (TPH) and aromatic amino acid decarboxylase (AADC) are expressed in taste cells. In contrast, enzymes necessary for NE synthesis, tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) are absent. Both TH and DBH are expressed in nerve fibers that penetrate taste buds. Taste buds also robustly express plasma membrane transporters for 5-HT and NE. Within the taste bud NET, a specific NE transporter, is expressed in some presynaptic (type III) and some glial-like (type I) cells but not in receptor (type II) cells. By using enzyme immunoassay, we show uptake of NE, probably through NET in taste epithelium. Proteins involved in inactivating and packaging NE, including catechol-O-methyltransferase (COMT), monoamine oxidase-A (MAO-A), vesicular monoamine transporter (VMAT1,2) and chromogranin A (ChrgA), are also expressed in taste buds. Within the taste bud, ChrgA is found only in presynaptic cells and may account for dense-cored vesicles previously seen in some taste cells. In summary, we postulate that aminergic presynaptic taste cells synthesize only 5-HT, whereas NE (perhaps secreted by sympathetic fibers) may be concentrated and repackaged for secretion

Independent Contributions of Discrete Dopaminergic Circuits to Cellular Plasticity, Memory Strength, and Valence in Drosophila

Summary: Dopaminergic neurons play a key role in encoding associative memories, but little is known about how these circuits modulate memory strength. Here we report that different sets of dopaminergic neurons projecting to the Drosophila mushroom body (MB) differentially regulate valence and memory strength. PPL2 neurons increase odor-evoked calcium responses to a paired odor in the MB and enhance behavioral memory strength when activated during olfactory classical conditioning. When paired with odor alone, they increase MB responses to the paired odor but do not drive behavioral approach or avoidance, suggesting that they increase the salience of the odor without encoding strong valence. This contrasts with the role of dopaminergic PPL1 neurons, which drive behavioral reinforcement but do not alter odor-evoked calcium responses in the MB when stimulated. These data suggest that different sets of dopaminergic neurons modulate olfactory valence and memory strength via independent actions on a memory-encoding brain region. : Boto et al. investigated the roles of two sets of dopaminergic neurons that converge on a memory-encoding brain region in flies. While one set, PPL1, drives aversive reinforcement (valence), PPL2 neurons enhance memory strength via modulation of Ca2+ response plasticity in memory-encoding mushroom body neurons. Keywords: learning, dopamine, PPL1, PPL2, valence, plasticit

Breadth of Tuning and Taste Coding in Mammalian Taste Buds

A longstanding question in taste research concerns taste coding and, in particular, how broadly are individual taste bud cells tuned to taste qualities (sweet, bitter, umami, salty, and sour). Taste bud cells express G-protein-coupled receptors for sweet, bitter, or umami tastes but not in combination. However, responses to multiple taste qualities have been recorded in individual taste cells. We and others have shown previously there are two classes of taste bud cells directly involved in gustatory signaling: “receptor” (type II) cells that detect and transduce sweet, bitter, and umami compounds, and “presynaptic” (type III) cells. We hypothesize that receptor cells transmit their signals to presynaptic cells. This communication between taste cells could represent a potential convergence of taste information in the taste bud, resulting in taste cells that would respond broadly to multiple taste stimuli. We tested this hypothesis using calcium imaging in a lingual slice preparation. Here, we show that receptor cells are indeed narrowly tuned: 82% responded to only one taste stimulus. In contrast, presynaptic cells are broadly tuned: 83% responded to two or more different taste qualities. Receptor cells responded to bitter, sweet, or umami stimuli but rarely to sour or salty stimuli. Presynaptic cells responded to all taste qualities, including sour and salty. These data further elaborate functional differences between receptor cells and presynaptic cells, provide strong evidence for communication within the taste bud, and resolve the paradox of broad taste cell tuning despite mutually exclusive receptor expression

Neurofibromin Loss of Function Drives Excessive Grooming in Drosophila

Neurofibromatosis I is a common genetic disorder that results in tumor formation, and predisposes individuals to a range of cognitive/behavioral symptoms, including deficits in attention, visuospatial skills, learning, language development, and sleep, and autism spectrum disorder-like traits. The nf1-encoded neurofibromin protein (Nf1) exhibits high conservation, from the common fruit fly, Drosophila melanogaster, to humans. Drosophila provides a powerful platform to investigate the signaling cascades upstream and downstream of Nf1, and the fly model exhibits similar behavioral phenotypes to mammalian models. In order to understand how loss of Nf1 affects motor behavior in flies, we combined traditional activity monitoring with video analysis of grooming behavior. In nf1 mutants, spontaneous grooming was increased up to 7x. This increase in activity was distinct from previously described dopamine-dependent hyperactivity, as dopamine transporter mutants exhibited slightly decreased grooming. Finally, we found that relative grooming frequencies can be compared in standard activity monitors that measure infrared beam breaks, enabling the use of activity monitors as an automated method to screen for grooming phenotypes. Overall, these data suggest that loss of nf1 produces excessive activity that is manifested as increased grooming, providing a platform to dissect the molecular genetics of neurofibromin signaling across neuronal circuits