Organization of an ascending circuit that conveys flight motor state in Drosophila.

Natural behaviors are a coordinated symphony of motor acts that drive reafferent (self-induced) sensory activation. Individual sensors cannot disambiguate exafferent (externally induced) from reafferent sources. Nevertheless, animals readily differentiate between these sources of sensory signals to carry out adaptive behaviors through corollary discharge circuits (CDCs), which provide predictive motor signals from motor pathways to sensory processing and other motor pathways. Yet, how CDCs comprehensively integrate into the nervous system remains unexplored. Here, we use connectomics, neuroanatomical, physiological, and behavioral approaches to resolve the network architecture of two pairs of ascending histaminergic neurons (AHNs) in Drosophila, which function as a predictive CDC in other insects. Both AHN pairs receive input primarily from a partially overlapping population of descending neurons, especially from DNg02, which controls wing motor output. Using Ca2+ imaging and behavioral recordings, we show that AHN activation is correlated to flight behavior and precedes wing motion. Optogenetic activation of DNg02 is sufficient to activate AHNs, indicating that AHNs are activated by descending commands in advance of behavior and not as a consequence of sensory input. Downstream, each AHN pair targets predominantly non-overlapping networks, including those that process visual, auditory, and mechanosensory information, as well as networks controlling wing, haltere, and leg sensorimotor control. These results support the conclusion that the AHNs provide a predictive motor signal about wing motor state to mostly non-overlapping sensory and motor networks. Future work will determine how AHN signaling is driven by other descending neurons and interpreted by AHN downstream targets to maintain adaptive sensorimotor performance.

Evidence of mirror therapy for recruitment of ipsilateral motor pathways in stroke recovery: A resting fMRI study.

Mirror therapy (MT) has been proposed to promote motor recovery post-stroke through activation of mirror neuron system, recruitment of ipsilateral motor pathways, or/and increasing attention toward the affected limb. However, neuroimaging evidence for these mechanisms is still lacking. To uncover the underlying mechanisms, we designed a randomized controlled study and used a voxel-based whole-brain analysis of resting-state fMRI to explore the brain reorganizations induced by MT. Thirty-five stroke patients were randomized to an MT group (n â€‹= â€‹16) and a conventional therapy (CT) group (n â€‹= â€‹19) for a 4-week intervention. Before and after the intervention, the Fugl-Meyer Assessment Upper Limb subscale (FMA-UL) and resting-state fMRI were collected. A healthy cohort (n â€‹= â€‹16) was established for fMRI comparison. The changes in fractional amplitude of low-frequency fluctuation (fALFF) and seed-based functional connectivity were analyzed to investigate the impact of intervention. Results showed that greater FMA-UL improvement in the MT group was associated with the compensatory increase of fALFF in the contralesional precentral gyrus (M1) region and the re-establishment of functional connectivity between the bilateral M1 regions, which facilitate motor signals transmission via the ipsilateral motor pathways from the ipsilesional M1, contralesional M1, to the affected limb. A step-wise linear regression model revealed these two brain reorganization patterns collaboratively contributed to FMA-UL improvement. In conclusion, MT achieved motor rehabilitation primarily by recruitment of the ipsilateral motor pathways. Trial Registration Information: http://www.chictr.org.cn. Unique Identifier. ChiCTR-INR-17013644, submitted on December 2, 2017.

Retrograde peripheral nerve regeneration from sensory to motor pathways in rats: a new experimental concept in nerve repair.

BACKGROUND: The polarity of nerve grafts does not interfere with axon growth. Our goal was to investigate whether axons can regenerate in a retrograde fashion within sensory pathways and then extend into motor pathways, leading to muscle reinnervation. METHODS: Fifty-four rats were randomized into four groups. In Group 1, the ulnar nerve was connected end-to-end to the superficial radial nerve after neurectomy of the radial nerve in the axilla. In Group 2, the ulnar nerve was connected end-to-end to the radial nerve distal to the humerus; the radial nerve then was divided in the axilla. In Group 3, the radial nerve was divided in the axilla, but no nerve reconstruction was performed. In Group 4, the radial nerve was crushed in the axilla. Over 6 months, we behaviorally assessed the recovery of toe spread in the right operated-upon forepaw by lifting the rat by its tail and lowering it onto a flat surface. Six months after surgery, rats underwent reoperation, nerve transfers were tested electrophysiologically, and the posterior interosseous nerve (PIN) was removed for histological evaluation. RESULTS: Rats in the crush group recovered toe spread between 5 and 8 days after surgery. Rats with nerve transfers demonstrated electrophysiological and histological findings of nerve regeneration but no behavioral recovery. CONCLUSIONS: Ulnar nerve axons regrew into the superficial radial nerve and then into the PIN to reinnervate the extensor digitorum communis. We were unable to demonstrate behavioral recovery because rats cannot readapt to cross-nerve transfer.

Cortical resting motor threshold difference in asleep-awake craniotomy for motor eloquent gliomas: WHO grading influences motor pathway excitability.

Developing neurophysiological tools to predict WHO tumor grade can empower the treating teams for a better surgical decision-making process. A total of 38 patients with supratentorial diffuse gliomas underwent an asleep-awake-sedated craniotomies for tumor removal with intraoperative neuromonitoring. The resting motor threshold was calculated for different train stimulation paradigms during awake and asleep phases. Receiver operating characteristic analysis and Bayesian regression models were performed to analyze the prediction of tumor grading based on the resting motor threshold differences. Significant positive spearman correlations were observed between resting motor threshold excitability difference and WHO tumor grade for train stimulation paradigms of 5 (R = 0.54, P = 0.00063), 4 (R = 0.49, P = 0.002), 3 (R = 0.51, P = 0.001), and 2 pulses (R = 0.54, P = 0.0007). Kruskal-Wallis analysis of the median revealed a positive significant difference between the median of excitability difference and WHO tumor grade in all paradigms. Receiver operating characteristic analysis showed 3 mA difference as the best predictor of high-grade glioma across different patterns of motor pathway stimulation. Bayesian regression found that an excitability difference above 3 mA would indicate a 75.8% probability of a glioma being high grade. Our results suggest that cortical motor excitability difference between the asleep and awake phases in glioma surgery could correlate with tumor grade.

Subcortical auditory model including efferent dynamic gain control with inputs from cochlear nucleus and inferior colliculus.

An auditory model has been developed with a time-varying, gain-control signal based on the physiology of the efferent system and subcortical neural pathways. The medial olivocochlear (MOC) efferent stage of the model receives excitatory projections from fluctuation-sensitive model neurons of the inferior colliculus (IC) and wide-dynamic-range model neurons of the cochlear nucleus. The response of the model MOC stage dynamically controls cochlear gain via simulated outer hair cells. In response to amplitude-modulated (AM) noise, firing rates of most IC neurons with band-enhanced modulation transfer functions in awake rabbits increase over a time course consistent with the dynamics of the MOC efferent feedback. These changes in the rates of IC neurons in awake rabbits were employed to adjust the parameters of the efferent stage of the proposed model. Responses of the proposed model to AM noise were able to simulate the increasing IC rate over time, whereas the model without the efferent system did not show this trend. The proposed model with efferent gain control provides a powerful tool for testing hypotheses, shedding insight on mechanisms in hearing, specifically those involving the efferent system.

The Application of Deep Brain Stimulation for Parkinson's Disease on the Motor Pathway: A Bibliometric Analysis across 10 Years.

BACKGROUND AND OBJECTIVE: Since its initial report by James Parkinson in 1817, Parkinson's disease (PD) has remained a central subject of research and clinical advancement. The disease is estimated to affect approximately 1% of adults aged 60 and above. Deep brain stimulation, emerging as an alternative therapy for end-stage cases, has offered a lifeline to numerous patients. This review aimed to analyze publications pertaining to the impact of deep brain stimulation on the motor pathway in patients with PD over the last decade. METHODS: Data were obtained from the Web of Science Core Collection through the library of Huazhong University of Science and Technology (China). The search strategy encompassed the following keywords: "deep brain stimulation", "Parkinson's disease", "motor pathway", and "human", from January 1, 2012, to December 1, 2022. Additionally, this review visualized the findings using the Citespace software. RESULTS: The results indicated that the United States, the United Kingdom, Germany, and China were the primary contributors to this research field. University College London, Capital Medical University, and Maastricht University were the top 3 research institutions in the research area. Tom Foltynie ranked first with 6 publications, and the journals of Brain and Brain Stimulation published the greatest number of relevant articles. The prevailing research focal points in this domain, as determined by keywords "burst analysis", "encompassed neuronal activity", "nucleus", "hyper direct pathway", etc. CONCLUSION: This study has provided a new perspective through bibliometric analysis of the deep brain stimulation therapy for treating patients with PD, which can shed light on future research to advance our comprehension of this particular field of study.

Internal feedback in the cortical perception-action loop enables fast and accurate behavior.

Animals move smoothly and reliably in unpredictable environments. Models of sensorimotor control, drawing on control theory, have assumed that sensory information from the environment leads to actions, which then act back on the environment, creating a single, unidirectional perception-action loop. However, the sensorimotor loop contains internal delays in sensory and motor pathways, which can lead to unstable control. We show here that these delays can be compensated by internal feedback signals that flow backward, from motor toward sensory areas. This internal feedback is ubiquitous in neural sensorimotor systems, and we show how internal feedback compensates internal delays. This is accomplished by filtering out self-generated and other predictable changes so that unpredicted, actionable information can be rapidly transmitted toward action by the fastest components, effectively compressing the sensory input to more efficiently use feedforward pathways: Tracts of fast, giant neurons necessarily convey less accurate signals than tracts with many smaller neurons, but they are crucial for fast and accurate behavior. We use a mathematically tractable control model to show that internal feedback has an indispensable role in achieving state estimation, localization of function (how different parts of the cortex control different parts of the body), and attention, all of which are crucial for effective sensorimotor control. This control model can explain anatomical, physiological, and behavioral observations, including motor signals in the visual cortex, heterogeneous kinetics of sensory receptors, and the presence of giant cells in the cortex of humans as well as internal feedback patterns and unexplained heterogeneity in neural systems.

Somatostatin-Expressing Neurons in the Ventral Tegmental Area Innervate Specific Forebrain Regions and Are Involved in Stress Response.

Expanding knowledge about the cellular composition of subcortical brain regions demonstrates large heterogeneity and differences from the cortical architecture. Previously we described three subtypes of somatostatin-expressing (Sst) neurons in the mouse ventral tegmental area (VTA) and showed their local inhibitory action on the neighboring dopaminergic neurons (Nagaeva et al., 2020). Here, we report that Sst+ neurons especially from the anterolateral part of the mouse VTA also project far outside the VTA and innervate forebrain regions that are mainly involved in the regulation of emotional behavior, including the ventral pallidum, lateral hypothalamus, the medial part of the central amygdala, anterolateral division of the bed nucleus of stria terminalis, and paraventricular thalamic nucleus. Deletion of these VTASst neurons in mice affected several behaviors, such as home cage activity, sensitization of locomotor activity to morphine, fear conditioning responses, and reactions to the inescapable stress of forced swimming, often in a sex-dependent manner. Together, these data demonstrate that VTASst neurons have selective projection targets distinct from the main targets of VTA dopamine neurons. VTASst neurons are involved in the regulation of behaviors primarily associated with the stress response, making them a relevant addition to the efferent VTA pathways and stress-related neuronal network.

Mapping subcortical motor pathways in humans with startle-conditioned TMS.

Subcortical motor pathways, such as the reticulospinal tract, are critical for producing and modulating voluntary movements and have been implicated in neurological conditions. Previous research has described the presence of ipsilateral motor evoked potentials (iMEPs) in the arm to transcranial magentic stimulation (TMS), and suggested they could be mediated by the uncrossed corticospinal tract or by ipsilateral cortico-reticulospinal connections. Here, we sought to elucidate the role of the reticulospinal tract in mediating iMEPs by assessing their modulation by a startling acoustic stimulus and mapping these responses across multiple upper limb effectors. In a first experiment, we delivered TMS at various intervals (1, 5, 10 and 15 ms) after a startling acoustic stimulus, known to excite the reticular formation, to elicit iMEPs in the arm. We observed robust facilitation of iMEP area when startle conditioning preceded TMS at the 10 ms interval. In a second experiment, we replicated our findings showing that both the area and number of iMEPs in the arm increases with startle conditioning. Using this technique, we observed that iMEPs are more prominent in the arm compared with the hand. In a third experiment, we also observed greater presence of iMEPs in flexor compared with extensor muscles. Together, these findings are consistent with properties of the reticulospinal tract observed in animals, suggesting that iMEPs primarily reflect reticulospinal activity. Our findings imply that we can use this approach to track modulation of cortico-reticulospinal excitability following interventions or neurological conditions where the reticulospinal tract may be involved in motor recovery.

Auditory Deprivation during Development Alters Efferent Neural Feedback and Perception.

Auditory experience plays a critical role in hearing development. Developmental auditory deprivation because of otitis media, a common childhood disease, produces long-standing changes in the central auditory system, even after the middle ear pathology is resolved. The effects of sound deprivation because of otitis media have been mostly studied in the ascending auditory system but remain to be examined in the descending pathway that runs from the auditory cortex to the cochlea via the brainstem. Alterations in the efferent neural system could be important because the descending olivocochlear pathway influences the neural representation of transient sounds in noise in the afferent auditory system and is thought to be involved in auditory learning. Here, we show that the inhibitory strength of the medial olivocochlear efferents is weaker in children with a documented history of otitis media relative to controls; both boys and girls were included in the study. In addition, children with otitis media history required a higher signal-to-noise ratio on a sentence-in-noise recognition task than controls to achieve the same criterion performance level. Poorer speech-in-noise recognition, a hallmark of impaired central auditory processing, was related to efferent inhibition, and could not be attributed to the middle ear or cochlear mechanics.SIGNIFICANCE STATEMENT Otitis media is the second most common reason children go to the doctor. Previously, degraded auditory experience because of otitis media has been associated with reorganized ascending neural pathways, even after middle ear pathology resolved. Here, we show that altered afferent auditory input because of otitis media during childhood is also associated with long-lasting reduced descending neural pathway function and poorer speech-in-noise recognition. These novel, efferent findings may be important for the detection and treatment of childhood otitis media.

Dynamic synchronization between hippocampal representations and stepping.

The hippocampus is a mammalian brain structure that expresses spatial representations1 and is crucial for navigation2,3. Navigation, in turn, intricately depends on locomotion; however, current accounts suggest a dissociation between hippocampal spatial representations and the details of locomotor processes. Specifically, the hippocampus is thought to represent mainly higher-order cognitive and locomotor variables such as position, speed and direction of movement4-7, whereas the limb movements that propel the animal can be computed and represented primarily in subcortical circuits, including the spinal cord, brainstem and cerebellum8-11. Whether hippocampal representations are actually decoupled from the detailed structure of locomotor processes remains unknown. To address this question, here we simultaneously monitored hippocampal spatial representations and ongoing limb movements underlying locomotion at fast timescales. We found that the forelimb stepping cycle in freely behaving rats is rhythmic and peaks at around 8 Hz during movement, matching the approximately 8 Hz modulation of hippocampal activity and spatial representations during locomotion12. We also discovered precisely timed coordination between the time at which the forelimbs touch the ground ('plant' times of the stepping cycle) and the hippocampal representation of space. Notably, plant times coincide with hippocampal representations that are closest to the actual position of the nose of the rat, whereas between these plant times, the hippocampal representation progresses towards possible future locations. This synchronization was specifically detectable when rats approached spatial decisions. Together, our results reveal a profound and dynamic coordination on a timescale of tens of milliseconds between central cognitive representations and peripheral motor processes. This coordination engages and disengages rapidly in association with cognitive demands and is well suited to support rapid information exchange between cognitive and sensory-motor circuits.

Pairing Transcranial Magnetic Stimulation and Loud Sounds Produces Plastic Changes in Motor Output.

Most current methods for neuromodulation target the cortex. Approaches for inducing plasticity in subcortical motor pathways, such as the reticulospinal tract, could help to boost recovery after damage (e.g., stroke). In this study, we paired loud acoustic stimulation (LAS) with transcranial magnetic stimulation (TMS) over the motor cortex in male and female healthy humans. LAS activates the reticular formation; TMS activates descending systems, including corticoreticular fibers. Two hundred paired stimuli were used, with 50 ms interstimulus interval at which LAS suppresses TMS responses. Before and after stimulus pairing, responses in the contralateral biceps muscle to TMS alone were measured. Ten, 20, and 30 min after stimulus pairing ended, TMS responses were enhanced, indicating the induction of LTP. No long-term changes were seen in control experiments which used 200 unpaired TMS or LAS, indicating the importance of associative stimulation. Following paired stimulation, no changes were seen in responses to direct corticospinal stimulation at the level of the medulla, or in the extent of reaction time shortening by a loud sound (StartReact effect), suggesting that plasticity did not occur in corticospinal or reticulospinal synapses. Direct measurements in female monkeys undergoing a similar paired protocol revealed no enhancement of corticospinal volleys after paired stimulation, suggesting no changes occurred in intracortical connections. The most likely substrate for the plastic changes, consistent with all our measurements, is an increase in the efficacy of corticoreticular connections. This new protocol may find utility, as it seems to target different motor circuits compared with other available paradigms.SIGNIFICANCE STATEMENT Induction of plasticity by neurostimulation protocols may be promising to enhance functional recovery after damage such as following stroke, but current protocols mainly target cortical circuits. In this study, we developed a novel paradigm which may generate long-term changes in connections between cortex and brainstem. This could provide an additional tool to modulate and improve recovery.

Afferent and efferent connections of the nucleus posterior tuberis in the firemouth cichlid, Thorichthys meeki.

The nucleus posterior tuberis (NPT) in teleost fishes, also called posterior tuberal nucleus, is situated in the posterior tuberculum of the diencephalon. It is fused across the midline and densely packed with small cells, but little is known about its connections. In this study, the afferent and efferent connections of the NPT were examined by means of tracer applications of the carbocyanine dye DiI in the firemouth cichlid, Thorichthys meeki. Retrogradely labeled cell bodies were found in the corpus mamillare and nucleus periventricularis of the inferior lobe; and anterogradely labeled terminal fibers were detected in the medial zone of the dorsal telencephalon, medial part of the nucleus lateralis tuberis, dorsal posterior thalamic nucleus, torus lateralis, medial part of the nucleus diffusus of the inferior lobe, and tectum opticum. All these connections show an ipsilateral tendency. The NPT is apparently a significant relay nucleus in the diencephalon of T. meeki, and possibly involved in a variety of feedback circuits. It seems also to be part of a tecto-hypothalamo-telencephalic pathway in cichlids.

Functional outcomes, extent of resection, and bright/vague fluorescence interface in resection of glioblastomas involving the motor pathways assisted by 5-ALA.

BACKGROUND: 5-Aminolevulinic acid (5-ALA) fluorescence can maximize perirolandic glioblastoma (GBM) resection with low rates of postoperative sequelae. Our purpose was to present the outcomes of our experience and compare them with other literature reports to investigate the potential influence of different intraoperative monitoring strategies and to evaluate the role of intraoperative data on neurological and radiological outcomes in our series. METHODS: We retrospectively analyzed our prospectively collected database of GBM involving the motor pathways. Each patient underwent tumor exeresis with intraoperative 5-ALA fluorescence visualization. Our monitoring strategy was based on direct stimulation (DS), combined with cortical or transcranial MEPs. The radiological outcome was evaluated with CRET vs. residual tumor, and the neurological outcome as improved, unchanged, or worsened. We also performed a literature review to compare our results with state-of-the-art on the subject. RESULTS: Sixty-five patients were included. CRET was 63.1%, permanent postoperative impairment was 1.5%, and DS's lowest motor threshold was 5 mA. In the literature, CRET was 25-73%, permanent postoperative impairment 3-16%, and DS lowest motor threshold was 1-3 mA. Our monitoring strategy identified a motor pathway in 60% of cases in faint fluorescent tissue, and its location in bright/faint fluorescence was predictive of CRET (p < 0.001). A preoperative motor deficit was associated with a worse clinical outcome (p < 0.001). Resection of bright fluorescent tissue was stopped in 26%, and fluorescence type of residual tumor was associated with higher CRET grades (p < 0.001). CONCLUSIONS: Based on the data presented and the current literature, distinct monitoring strategies can achieve different onco-functional outcomes in 5-ALA-guided resection of a glioblastoma (GBM) motor pathway. Intraoperatively, functional and fluorescence data close to a bright/vague interface could be helpful to predict onco-functional outcomes.

Evaluation of Medial Olivocochlear Neural Efferent Pathway in Tinnitus Perception in Normal-hearing Individuals.

OBJECTIVE: The objective of this study is to investigate a possible role of the Medial Olivocochlear (MOC) efferent neural pathway and neural connections responsible for tinnitus generation in silence/sensory deprivation. DESIGN: By placing normal hearing participants in a sound booth for 10 minutes, silence/sensory deprivation was created. This offered assessment of MOC neural pathway in normal hearing participants in silence. Hyperactivity of MOC neural pathway was assessed by its more suppressive effect on Transient Otoacoustic Emissions (TEOAEs) in silence. The required auditory measurements were recorded in the sound booth using recommended diagnostic protocols to ensure the effect of 'only silence' on auditory structures. TEOAE were recorded from the right ear and suppression was measured by placing noise in the left ear. Fifty-eight normal hearing male individuals between age 18-35 years were recruited as participants in this study. RESULTS: Approximately, forty-one percent of the participants perceived some type of tinnitus during/after 10 minutes of silence. No statistically significant difference was found in the total TEOAE amplitude and TEOAE suppression amplitude before and after ten minutes of silence. Post silence total TEOAE suppression between tinnitus perceiving and non-perceiving tinnitus participants were not statistically significantly different. CONCLUSION: These results suggest that the medial olivocochlear efferent pathway or lower brain stem area does not appear to play a role in the emergence of temporary tinnitus in silence however indicate the involvement of higher central auditory nervous system structures in perception of the tinnitus which support the well-accepted notion that tinnitus is the central auditory processing phenomenon.

Hiperacusia en trastornos del espectro autista: una revisión de la literatura / Hyperacusis in autism spectrum disorders: a review of the literature

Resumen La hiperacusia se define como la intolerancia a ciertos sonidos cotidianos que causa angustia y discapacidad significativas en las actividades sociales, ocupacionales, recreativas y otras actividades cotidianas. Los sonidos pueden percibirse como incómodamente fuertes, desagradables, atemorizantes o dolorosos. Se encuentra presente en aproximadamente un 3% población general, y aumenta significativamente en trastornos del espectro autista (TEA), alcanzando entre un 15% a 40%. Los mecanismos fisiopatológicos no son del todo claros, pero se ha propuesto, una alteración en el funcionamiento de mecanismos reflejos y de regulación, tanto a nivel de la vía auditiva periférica, como central, incluyendo estructuras no relacionadas directamente con la vía auditiva. El siguiente texto tiene como objetivo analizar la relación entre hiperacusia y TEA, enfatizando en la frecuencia en que se presentan como comorbilidades, en los posibles mecanismos fisiopatológicos, y en actualizaciones en el abordaje diagnóstico y terapéutico. Se realiza una revisión bibliográfica cualitativa en Pubmed con artículos entre los años 2008-2020 utilizando los términos: "hyperacusis autism", "sistema olivococlear", arrojando 39 artículos, de los cuales se seleccionaron en base a la temática de cada uno, evaluada por los autores. A pesar de una significativa relación entre hiperacusia y TEA, los mecanismos fisiopatológicos de ambas patologías siguen siendo un misterio. Existen estudios que sugieren pruebas de screening no invasivas que relacionan ambas patologías, pero debido a los sesgos de selección, todavía no son factibles de usar en forma universal. El abordaje terapéutico ha sido poco explorado, y no se dispone de fármacos que hayan demostrado su efectividad, por el contrario, algunos de ellos empeoran la sintomatología. Se recomienda al tratante, seguir un camino largo, en conjunto con el paciente, donde las terapias no farmacológicas como la terapia cognitivo conductual han mostrado tener buenos resultados.

Abstract Hyperacusis is defined as intolerance to certain sounds that causes significant distress and disability in social, occupational, recreational and other activities. Sounds can be perceived as uncomfortably loud, unpleasant, frightening, or painful. It is present in approximately 3% of the general population, and increases significantly in autism spectrum disorders (ASD), between 15% and 40%. The pathophysiological mechanisms are not entirely clear, but an alteration in the functioning of reflex and regulatory mechanisms has been proposed, both at the peripheral and central auditory pathways, including structures not directly related to the auditory pathway. The therapeutic approach has been little explored as there are no drugs that have demonstrated their effectiveness, on the contrary, some of them worsen the symptoms. The practitioner is recommended to follow a long path, in conjunction with the patient, where non-pharmacological therapies such as cognitive behavioral therapy have been shown to have good results. The following text shows a review of the literature with articles referring to the subject between the years 2008-2019.

Central circuitry and function of the cochlear efferent systems.

The cochlear efferent system comprises multiple populations of brainstem neurons whose axons project to the cochlea, and whose responses to acoustic stimuli lead to regulation of auditory sensitivity. The major groups of efferent neurons are found in the superior olivary complex and are likely activated by neurons of the cochlear nucleus, thus forming a simple reflex pathway back to the cochlea. The peripheral actions of only one of these efferent cell types has been well described. Moreover, the efferent neurons are not well understood at the cellular- and circuit-levels. For example, ample demonstration of descending projections to efferent neurons raises the question of whether these additional inputs constitute a mechanism for modulation of relay function or instead play a more prominent role in driving the efferent response. Related to this is the question of synaptic plasticity at these synapses, which has the potential to differentially scale the degree of efferent activation across time, depending on the input pathway. This review will explore central nervous system aspects of the efferent system, the physiological properties of the neurons, their synaptic inputs, their modulation, and the effects of efferent axon collaterals within the brainstem.

Easy and Hard Auditory Tasks Distinguished by Otoacoustic Emissions and Event-related Potentials: Insights into Efferent System Activity.

The medial olivocochlear (MOC) system is thought to be responsible for modulation of peripheral hearing through descending (efferent) pathways. This study investigates the connection between peripheral hearing function and auditory attention tasks of different degrees of difficulty. Peripheral hearing function was evaluated by analyzing the amount of change in otoacoustic emissions (OAEs) by contralateral acoustic stimulation (CAS), a well-known effect of the MOC system. Simultaneously, levels of attention were evaluated by event-related potentials (ERPs). The ERPs showed clear differences in processing tasks of different difficulty, but paradoxically there was no difference in the amount of OAE change brought about by CAS. There was also no effect on OAE latency, nor was there any difference in noise level or number of rejected trials. However, we observed that the changes in OAEs by CAS for easy and hard tasks were correlated with the magnitude of the P3 wave in the ERP. This suggests there might be some sort of mutual compensation mechanism - presently unknown - between periphery and cortex.

Whole-brain mapping of efferent projections of the anterior cingulate cortex in adult male mice.

The anterior cingulate cortex (ACC) is a key cortical region that plays an important role in pain perception and emotional functions. Previous studies of the ACC projections have been collected primarily from monkeys, rabbits and rats. Due to technological advances, such as gene manipulation, recent progress has been made in our understanding of the molecular and cellular mechanisms of the ACC-related chronic pain and emotion is mainly obtained from adult mice. Few anatomic studies have examined the whole-brain projections of the ACC in adult mice. In the present study, we examined the continuous axonal outputs of the ACC in the whole brain of adult male mice. We used the virus anterograde tracing technique and an ultrahigh-speed imaging method of Volumetric Imaging with Synchronized on-the-fly-scan and Readout (VISoR). We created a three-dimensional (3D) reconstruction of mouse brains. We found that the ACC projected ipsilaterally primarily to the caudate putamen (CPu), ventral thalamic nucleus, zona incerta (ZI), periaqueductal gray (PAG), superior colliculus (SC), interpolar spinal trigeminal nucleus (Sp5I), and dorsal medullary reticular nucleus (MdD). The ACC also projected to contralateral brain regions, including the ACC, reuniens thalamic nucleus (Re), PAG, Sp5I, and MdD. Our results provide a whole-brain mapping of efferent projections from the ACC in adult male mice, and these findings are critical for future studies of the molecular and synaptic mechanisms of the ACC and its related network in mouse models of brain diseases.