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.

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.

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.

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.

Histamine receptors rapidly desensitize without altering nerve-evoked contractions in murine urinary bladder smooth muscle.

Histamine has been implicated in urinary bladder dysfunction as an inflammatory mediator driving sensory nerve hypersensitivity. However, the direct influence of histamine on smooth muscle has not been thoroughly investigated. We hypothesized that histamine directly contracts urinary bladder smooth muscle (UBSM) independent of effects on nerves. Single cell quantitative RT-PCR determined that only histamine H1 and H2 receptors were expressed on UBSM cells. In isolated tissue bath experiments, histamine (200 µM) caused a highly variable and rapidly desensitizing contraction that was completely abolished by the H1 receptor antagonist fexofenadine (5 µM) and the Gq/11 inhibitor YM254890 (1 µM). Neither the muscarinic receptor antagonist atropine (1 µM), the Na+ channel blocker tetrodotoxin (1 µM), nor the transient receptor potential vanilloid type 1 antagonist capsazepine (10 µM) altered responses to histamine, suggesting that nerve activation was not involved. UBSM desensitization to histamine was not due to receptor internalization, as neither the cholesterol-depleting agent methyl-ß-cyclodextrin (10 mM), the dynamin-mediated endocytosis inhibitor dynasore (100 µM), nor the clathrin-mediated endocytosis inhibitor pitstop2 (15 µM) augmented or prolonged histamine contractions. Buffer from desensitized tissues still contracted histamine-naïve tissues, revealing that histamine was not metabolized. Prolonged exposure to histamine also had no effect on contractions due to electrical field stimulation, suggesting that both efferent nerve and UBSM excitability were unchanged. Together, these data suggest that histamine, although able to transiently contract UBSM, does not have a lasting effect on UBSM excitability or responses to efferent nerve input. Thus, any acute effects of histamine directly on UBSM contractility are unlikely to alter urinary bladder function.NEW & NOTEWORTHY Histamine is commonly associated with inflammatory bladder pathologies. We sought to investigate the role of histamine on urinary bladder contractility. Histamine contracts the bladder, but this response is highly variable and desensitizes completely in minutes. This desensitization is not due to internalization of the receptor or metabolism of histamine. Because nerve-evoked contractions are also not increased in the presence of histamine, our findings suggest that histamine is not directly acting to change contractility.

Intersectional genetic tools to study skilled reaching in mice.

Reaching to grasp is an evolutionarily conserved behavior and a crucial part of the motor repertoire in mammals. As it is studied in the laboratory, reaching has become the prototypical example of dexterous forelimb movements, illuminating key principles of motor control throughout the spinal cord, brain, and peripheral nervous system. Here, we (1) review the motor elements or phases that comprise the reach, grasp, and retract movements of reaching behavior, (2) highlight the role of intersectional genetic tools in linking these movements to their neuronal substrates, (3) describe spinal cord cell types and their roles in skilled reaching, and (4) how descending pathways from the brain and the sensory systems contribute to skilled reaching. We emphasize that genetic perturbation experiments can pin-point the neuronal substrates of specific phases of reaching behavior.

A Cortico-Cortical Pathway Targets Inhibitory Interneurons and Modulates Paw Movement during Locomotion in Mice.

The primary somatosensory cortex (S1) is important for the control of movement as it encodes sensory input from the body periphery and external environment during ongoing movement. Mouse S1 consists of several distinct sensorimotor subnetworks that receive topographically organized corticocortical inputs from distant sensorimotor areas, including the secondary somatosensory cortex (S2) and primary motor cortex (M1). The role of the vibrissal S1 area and associated cortical connections during active sensing is well documented, but whether (and if so, how) non-whisker S1 areas are involved in movement control remains relatively unexplored. Here, we demonstrate that unilateral silencing of the non-whisker S1 area in both male and female mice disrupts hind paw movement during locomotion on a rotarod and a runway. S2 and M1 provide major long-range inputs to this S1 area. Silencing S2→non-whisker S1 projections alters the hind paw orientation during locomotion, whereas manipulation of the M1 projection has little effect. Using patch-clamp recordings in brain slices from male and female mice, we show that S2 projection preferentially innervates inhibitory interneuron subtypes. We conclude that interneuron-mediated S2-S1 corticocortical interactions are critical for efficient locomotion.SIGNIFICANCE STATEMENT Somatosensory cortex participates in controlling rhythmic movements, such as whisking and walking, but the neural circuitry underlying movement control by somatosensory cortex remains relatively unexplored. We uncover a corticocortical circuit in primary somatosensory cortex that regulates paw orientation during locomotion in mice. We identify neuronal elements that comprise these cortical pathways using pharmacology, behavioral assays, and circuit-mapping methods.

Olivocochlear efferent effects on perception and behavior.

The role of the mammalian auditory olivocochlear efferent system in hearing has long been the subject of debate. Its ability to protect against damaging noise exposure is clear, but whether or not this is the primary function of a system that evolved in the absence of industrial noise remains controversial. Here we review the behavioral consequences of olivocochlear activation and diminished olivocochlear function. Attempts to demonstrate a role for hearing in noise have yielded conflicting results in both animal and human studies. A role in selective attention to sounds in the presence of distractors, or attention to visual stimuli in the presence of competing auditory stimuli, has been established in animal models, but again behavioral studies in humans remain equivocal. Auditory processing deficits occur in models of congenital olivocochlear dysfunction, but these deficits likely reflect abnormal central auditory development rather than direct effects of olivocochlear feedback. Additional proposed roles in age-related hearing loss, tinnitus, hyperacusis, and binaural or spatial hearing, are intriguing, but require additional study. These behavioral studies almost exclusively focus on medial olivocochlear effects, and many relied on lesioning techniques that can have unspecific effects. The consequences of lateral olivocochlear and of corticofugal pathway activation for perception remain unknown. As new tools for targeted manipulation of olivocochlear neurons emerge, there is potential for a transformation of our understanding of the role of the olivocochlear system in behavior across species.

Role of astrocytes in rhythmic motor activity.

Rhythmic motor activities such as breathing, locomotion, tremor, or mastication are organized by groups of interconnected neurons. Most synapses in the central nervous system are in close apposition with processes belonging to astrocytes. Neurotransmitters released from neurons bind to receptors expressed by astrocytes, activating a signaling pathway that leads to an increase in calcium concentration and the release of gliotransmitters that eventually modulate synaptic transmission. It is therefore likely that the activation of astrocytes impacts motor control. Here we review recent studies demonstrating that astrocytes inhibit, modulate, or trigger motor rhythmic behaviors.

The medial olivocochlear reflex strength is modulated during a visual working memory task.

Top-down modulation of sensory responses to distracting stimuli by selective attention has been proposed as an important mechanism by which our brain can maintain relevant information during working memory tasks. Previous works in visual working memory (VWM) have reported modulation of neural responses to distracting sounds at different levels of the central auditory pathways. Whether these modulations occur also at the level of the auditory receptor is unknown. Here, we hypothesize that cochlear responses to irrelevant auditory stimuli can be modulated by the medial olivocochlear system during VWM. Twenty-one subjects (13 males, mean age 25.3 yr) with normal hearing performed a visual change detection task with different VWM load conditions (high load = 4 visual objects; low load = 2 visual objects). Auditory stimuli were presented as distractors and allowed the measurement of distortion product otoacoustic emissions (DPOAEs) and scalp auditory evoked potentials. In addition, the medial olivocochlear reflex strength was evaluated by adding contralateral acoustic stimulation. We found larger contralateral acoustic suppression of DPOAEs during the visual working memory period (n = 21) compared with control experiments (n = 10), in which individuals were passively exposed to the same experimental conditions. These results show that during the visual working memory period there is a modulation of the medial olivocochlear reflex strength, suggesting a possible common mechanism for top-down filtering of auditory responses during cognitive processes.NEW & NOTEWORTHY The auditory efferent system has been proposed to function as a biological filter of cochlear responses during selective attention. Here, we recorded electroencephalographic activity and otoacoustic emissions in response to auditory distractors during a visual working memory task in humans. We found that the olivocochlear efferent activity is modulated during the visual working memory period suggesting a common mechanism for suppressing cochlear responses during selective attention and working memory.

Efferent feedback controls bilateral auditory spontaneous activity.

In the developing auditory system, spontaneous activity generated in the cochleae propagates into the central nervous system to promote circuit formation. The effects of peripheral firing patterns on spontaneous activity in the central auditory system are not well understood. Here, we describe wide-spread bilateral coupling of spontaneous activity that coincides with the period of transient efferent modulation of inner hair cells from the brainstem medial olivocochlear system. Knocking out α9/α10 nicotinic acetylcholine receptors, a requisite part of the efferent pathway, profoundly reduces bilateral correlations. Pharmacological and chemogenetic experiments confirm that the efferent system is necessary for normal bilateral coupling. Moreover, auditory sensitivity at hearing onset is reduced in the absence of pre-hearing efferent modulation. Together, these results demonstrate how afferent and efferent pathways collectively shape spontaneous activity patterns and reveal the important role of efferents in coordinating bilateral spontaneous activity and the emergence of functional responses during the prehearing period.

Enhanced structural connectivity within the motor loop in professional boxers prior to a match.

Professional boxers train to reduce their body mass before a match to refine their body movements. To test the hypothesis that the well-defined movements of boxers are represented within the motor loop (cortico-striatal circuit), we first elucidated the brain structure and functional connectivity specific to boxers and then investigated plasticity in relation to boxing matches. We recruited 21 male boxers 1 month before a match (Time1) and compared them to 22 age-, sex-, and body mass index (BMI)-matched controls. Boxers were longitudinally followed up within 1 week prior to the match (Time2) and 1 month after the match (Time3). The BMIs of boxers significantly decreased at Time2 compared with those at Time1 and Time3. Compared to controls, boxers presented significantly higher gray matter volume in the left putamen, a critical region representing motor skill training. Boxers presented significantly higher functional connectivity than controls between the left primary motor cortex (M1) and left putamen, which is an essential region for establishing well-defined movements. Boxers also showed significantly higher structural connectivity in the same region within the motor loop from Time1 to Time2 than during other periods, which may represent the refined movements of their body induced by training for the match.

Astrocytes close a motor circuit critical period.

Critical periods-brief intervals during which neural circuits can be modified by activity-are necessary for proper neural circuit assembly. Extended critical periods are associated with neurodevelopmental disorders; however, the mechanisms that ensure timely critical period closure remain poorly understood1,2. Here we define a critical period in a developing Drosophila motor circuit and identify astrocytes as essential for proper critical period termination. During the critical period, changes in activity regulate dendrite length, complexity and connectivity of motor neurons. Astrocytes invaded the neuropil just before critical period closure3, and astrocyte ablation prolonged the critical period. Finally, we used a genetic screen to identify astrocyte-motor neuron signalling pathways that close the critical period, including Neuroligin-Neurexin signalling. Reduced signalling destabilized dendritic microtubules, increased dendrite dynamicity and impaired locomotor behaviour, underscoring the importance of critical period closure. Previous work defined astroglia as regulators of plasticity at individual synapses4; we show here that astrocytes also regulate motor circuit critical period closure to ensure proper locomotor behaviour.

Transcranial Random Noise Stimulation Acutely Lowers the Response Threshold of Human Motor Circuits.

Transcranial random noise stimulation (tRNS) over cortical areas has been shown to acutely improve performance in sensory detection tasks. One explanation for this behavioral effect is stochastic resonance (SR), a mechanism that explains how signal processing in nonlinear systems can benefit from added noise. While acute noise benefits of electrical RNS have been demonstrated at the behavioral level as well as in in vitro preparations of neural tissue, it is currently largely unknown whether similar effects can be shown at the neural population level using neurophysiological readouts of human cortex. Here, we hypothesized that acute tRNS will increase the responsiveness of primary motor cortex (M1) when probed with transcranial magnetic stimulation (TMS). Neural responsiveness was operationalized via the well-known concept of the resting motor threshold (RMT). We showed that tRNS acutely decreases RMT. This effect was small, but it was consistently replicated across four experiments including different cohorts (total N = 81, 46 females, 35 males), two tRNS electrode montages, and different control conditions. Our experiments provide critical neurophysiological evidence that tRNS can acutely generate noise benefits by enhancing the neural population response of human M1.SIGNIFICANCE STATEMENT A hallmark feature of stochastic resonance (SR) is that signal processing can benefit from added noise. This has mainly been demonstrated at the single-cell level in vitro where the neural response to weak input signals can be enhanced by simultaneously applying random noise. Our finding that transcranial random noise stimulation (tRNS) acutely increases the excitability of corticomotor circuits extends the principle of noise benefits to the neural population level in human cortex. Our finding is in line with the notion that tRNS might affect cortical processing via the SR phenomenon. It suggests that enhancing the response of cortical populations to an external stimulus might be one neurophysiological mechanism mediating performance improvements when tRNS is applied to sensory cortex during perception tasks.

Reafference and the origin of the self in early nervous system evolution.

Discussions of the function of early nervous systems usually focus on a causal flow from sensors to effectors, by which an animal coordinates its actions with exogenous changes in its environment. We propose, instead, that much early sensing was reafferent; it was responsive to the consequences of the animal's own actions. We distinguish two general categories of reafference-translocational and deformational-and use these to survey the distribution of several often-neglected forms of sensing, including gravity sensing, flow sensing and proprioception. We discuss sensing of these kinds in sponges, ctenophores, placozoans, cnidarians and bilaterians. Reafference is ubiquitous, as ongoing action, especially whole-body motility, will almost inevitably influence the senses. Corollary discharge-a pathway or circuit by which an animal tracks its own actions and their reafferent consequences-is not a necessary feature of reafferent sensing but a later-evolving mechanism. We also argue for the importance of reafferent sensing to the evolution of the body-self, a form of organization that enables an animal to sense and act as a single unit. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.

Efference copy in kinesthetic perception: a copy of what is it?

A number of notions in the fields of motor control and kinesthetic perception have been used without clear definitions. In this review, we consider definitions for efference copy, percept, and sense of effort based on recent studies within the physical approach, which assumes that the neural control of movement is based on principles of parametric control and involves defining time-varying profiles of spatial referent coordinates for the effectors. The apparent redundancy in both motor and perceptual processes is reconsidered based on the principle of abundance. Abundance of efferent and afferent signals is viewed as the means of stabilizing both salient action characteristics and salient percepts formalized as stable manifolds in high-dimensional spaces of relevant elemental variables. This theoretical scheme has led recently to a number of novel predictions and findings. These include, in particular, lower accuracy in perception of variables produced by elements involved in a multielement task compared with the same elements in single-element tasks, dissociation between motor and perceptual effects of muscle coactivation, force illusions induced by muscle vibration, and errors in perception of unintentional drifts in performance. Taken together, these results suggest that participation of efferent signals in perception frequently involves distorted copies of actual neural commands, particularly those to antagonist muscles. Sense of effort is associated with such distorted efferent signals. Distortions in efference copy happen spontaneously and can also be caused by changes in sensory signals, e.g., those produced by muscle vibration.

Differential efferent projections of GABAergic neurons in the basolateral and central nucleus of amygdala in mice.

The Basolateral amygdala (BLA) and central nucleus of the amygdala (CEA) have been proved to play a key role in the control of anxiety, stress and fear-related behaviors. BLA is a cortex-like complex consisting of both γ-aminobutyric acidergic (GABAergic) interneurons and glutamatergic neurons. The CEA is a striatum-like output of the amygdala, consisting almost exclusively of GABAergic medium spiny neurons. In this study, we explored the morphology and axonal projections of the GABAergic neurons in BLA and CEA, using conditional anterograde axonal tracing, immunohistochemistry, and VGAT-Cre transgenic mice to further understand their functional roles. We found that the axonal projections of GABAergic neurons from the BLA mainly distributed to the forebrain, whilst GABAergic neurons from the CEA distributed to the forebrain, midbrain and brainstem. In the forebrain, the axonal projections of GABAergic neurons from the BLA projected to the anterior olfactory nucleus, the cerebral cortex, the septum, the striatum, the thalamus, the amygdala and the hippocampus. The axonal projections of GABAergic neurons from the CEA distributed to the nuclei of the prefrontal cortex, the bed nucleus of the stria terminalis, the hypothalamus and the thalamus. In the midbrain and brainstem, the axonal projections of GABAergic neurons from the CEA were found in the periaqueductal gray, the substantia nigra, and the locus coeruleus. These data reveal the neuroanatomical basis for exploring the function of GABAergic neurons in the BLA and CEA, particularly during the processing of fear-related behavior.

Acoustic Reflexes in Aural Atresia Patients: Evidence of an Intact Efferent System?

OBJECTIVE: To record crossed acoustic reflex thresholds (xART's) postoperatively from patients after surgical repair of unilateral congenital aural atresia (CAA). To seek explanations for when xARTs can and cannot be recorded. We hope to understand the implications for this central auditory reflex despite early afferent deprivation. METHODS: Patients who underwent surgery to correct unilateral CAA at a tertiary academic medical were prospectively enrolled to evaluate for the presence of xART. Preoperative ARTs in the normal (non-atretic) ear, and postoperative ipsilateral ARTs (stimulus in the normal ear) and contralateral ARTs (stimulus in the newly reconstructed atretic ear; record in the normal ear) were measured at 500, 1000, and 2000 Hz. RESULTS: Four of 11 patients with normal ipsilateral reflex thresholds preoperatively demonstrated crossed acoustic reflexes postoperatively (stimulus in reconstructed ear; record from normal ear). Four other patients demonstrated normal ipsilateral thresholds preoperatively but did not have crossed reflexes postoperatively. No reflexes (pre- or postoperatively) could be recorded in 3 patients. Crossed reflex threshold is significantly correlated with the postoperative audiometric threshold. There was no correlation between ipsilateral and contralateral reflex thresholds. CONCLUSION: Crossed acoustic reflexes can be recorded from some but not all postoperative atresia patients, and the thresholds for those reflexes correlate with the postoperative pure tone threshold. The presence of acoustic reflexes implies an intact CN VIII-to-opposite CN VII central reflex arc despite early unilateral sound deprivation.

Olfaction in Lamprey Pallium Revisited-Dual Projections of Mitral and Tufted Cells.

The presence of two separate afferent channels from the olfactory glomeruli to different targets in the brain is unravelled in the lamprey. The mitral-like cells send axonal projections directly to the piriform cortex in the ventral part of pallium, whereas the smaller tufted-like cells project separately and exclusively to a relay nucleus called the dorsomedial telencephalic nucleus (dmtn). This nucleus, located at the interface between the olfactory bulb and pallium, in turn projects to a circumscribed area in the anteromedial, ventral part of pallium. The tufted-like cells are activated with short latency from the olfactory nerve and terminate with mossy fibers on the dmtn cells, wherein they elicit large unitary excitatory postsynaptic potentials (EPSPs). In all synapses along this tufted-like cell pathway, there is no concurrent inhibition, in contrast to the mitral-like cell pathway. This is similar to recent findings in rodents establishing two separate exclusive projection patterns, suggesting an evolutionarily conserved organization.