Zebrafish models are used increasingly to study the molecular pathogenesis of Parkinson's disease (PD), owing to the extensive array of techniques available for their experimental manipulation and analysis. The ascending dopaminergic projection from the posterior tuberculum (TPp; diencephalic populations DC2 and DC4) to the subpallium is considered the zebrafish correlate of the mammalian nigrostriatal projection, but little is known about the neurophysiology of zebrafish DC2/4 neurons. This is an important knowledge gap, because autonomous activity in mammalian substantia nigra (SNc) dopaminergic neurons contributes to their vulnerability in PD models. Using a new transgenic zebrafish line to label living dopaminergic neurons, and a novel brain slice preparation, we conducted whole-cell patch clamp recordings of DC2/4 neurons from adult zebrafish of both sexes. Zebrafish DC2/4 neurons share many physiological properties with mammalian dopaminergic neurons, including the cell-autonomous generation of actio...

At the request of the authors, The Journal of Neuroscience is retracting “The Sustained Antidepressant Effects of Ketamine are Independent of the Lateral Habenula,” by Xuelong Zhou, Chenjing Zhang, Jiamin Miao, Ziyang Chen, Hongquan Dong, and Cunming Liu, which appears on pages [4131–4140][1]

We have previously established that PV+ neurons and Npas1+ neurons are distinct neuron classes in the external globus pallidus (GPe): they have different topographical, electrophysiological, circuit, and functional properties. Aside from Foxp2+ neurons, which are a unique subclass within the Npas1+ class, we lack driver lines that effectively capture other GPe neuron subclasses. In this study, we examined the utility of Kcng4-Cre, Npr3-Cre, and Npy2r-Cre mouse lines (both males and females) for the delineation of GPe neuron subtypes. By using these novel driver lines, we have provided the most exhaustive investigation of electrophysiological studies of GPe neuron subtypes to date. Corroborating our prior studies, GPe neurons can be divided into two statistically distinct clusters that map onto PV+ and Npas1+ classes. By combining optogenetics and machine learning-based tracking, we showed that optogenetic perturbation of GPe neuron subtypes generated unique behavioral structures. Our findings further highl...

The Coronavirus Disease - 2019 (COVID-19) presents a variability of clinical symptoms, ranging from asymptomatic to severe respiratory and systemic conditions. In a cohort of patients, the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), beyond the classical respiratory manifestations, induces anosmia. Evidence has suggested SARS-CoV-2-induced anosmia can be the result of neurodegeneration of the olfactory pathway. Neurological symptoms associated with COVID-19 have been reported; however, the precise mechanism and possible long-lasting effects remain poorly investigated. Preclinical models are valuable tools for describing and testing new possible treatments for neurological disorders. In this way, the zebrafish ( Danio rerio ) organism model represents an attractive tool in the field of neuroscience, showing economic and logistical advantages besides genetic and physiologic similarities with mammalian, including the brain structure and functions. Besides, its external embryonic development, hi...

Age-related hearing loss is the most prevalent sensory impairment in the older adult population and is related to noise-induced damage or age-related deterioration of the peripheral auditory system. Hearing loss may affect the central auditory pathway in the brain, which is a continuation of the peripheral auditory system located in the ear. A debilitating symptom that frequently co-occurs with hearing loss is tinnitus. Strikingly, investigations into the impact of acquired hearing loss, with and without tinnitus, on the human central auditory pathway are sparse. This study used diffusion-weighted imaging (DWI) to investigate changes in the largest central auditory tract, the acoustic radiation, related to hearing loss and tinnitus. Participants with hearing loss, with and without tinnitus, and a control group were included. Both conventional diffusion tensor analysis and higher-order fixel-based analysis were applied. The fixel-based analysis was used as a novel framework providing insight into the axonal...

Drosophila odorant receptors (Ors) are ligand gated ion channels composed of a common receptor subunit Or co-receptor (ORCO) and one of 62 “tuning” receptor subunits that confer odorant specificity to olfactory neuron responses. Like other sensory systems studied to date, exposing Drosophila olfactory neurons to activating ligands results in reduced responses to subsequent exposures through a process called desensitization. We recently showed that phosphorylation of serine 289 on the common Or subunit ORCO is required for normal peak olfactory neuron responses. Dephosphorylation of this residue occurs on prolonged odorant exposure, and underlies the slow modulation of olfactory neuron responses we term “slow desensitization.” Slow desensitization results in the reduction of peak olfactory neuron responses and flattening of dose–response curves, implicating changes in ORCOS289 phosphorylation state as an important modulator of olfactory neuron responses. Here, we report the identification of the primary kin...

Memories are rarely acquired under ideal conditions, rendering them vulnerable to profound omissions, errors, and ambiguities. Consistent with this, recent work using context fear conditioning has shown that memories formed after inadequate learning time display a variety of maladaptive properties, including overgeneralization to similar contexts. However, the neuronal basis of such poor learning and memory imprecision remains unknown. Using c-fos to track neuronal activity in male mice, we examined how these learning-dependent changes in context fear memory precision are encoded in hippocampal ensembles. We found that the total number of c-fos-encoding cells did not correspond with learning history but instead more closely reflected the length of the session immediately preceding c-fos measurement. However, using a c-fos-driven tagging method ( TRAP2 mouse line), we found that the degree of learning and memory specificity corresponded with neuronal activity in a subset of dentate gyrus cells that were act...

Ketamine is known to have a rapid and lasting antidepressant effect. Recent studies have shown that ketamine exerts it rapid antidepressant effect by blocking burst firing in the lateral habenula (LHb). Whether the sustained antidepressant effect of ketamine occurs through the same mechanism has not been explored. Here, using male rats, we found that local infusion of (R,S)-ketamine into the LHb resulted in a rapid antidepressant-like effect 1 h after infusion, which almost returned to baseline levels after 24 h. Intra-LHb injection of (S)-ketamine also showed a significant antidepressant-like effect 1 h after injection, which recovered at 24 h. No significant antidepressant-like effect was found at 1 or 24 h after the administration of (R)-ketamine into the LHb. Injection of (2R,6R)-hydroxynorketamine, a ketamine metabolite, into the LHb did not result in any obvious antidepressant-like effect 1 or 24 h after injection. Systemic administration of (R,S)-ketamine (intraperitoneally) significantly suppressed...

The planning and execution of head-beak movements are vital components of bird behavior. They require integration of sensory input and internal processes with goal-directed motor output. Despite its relevance, the neurophysiological mechanisms underlying action planning and execution outside of the song system are largely unknown. We recorded single-neuron activity from the associative endbrain area nidopallium caudolaterale (NCL) of two male carrion crows ( Corvus corone ) trained to plan and execute head-beak movements in a spatial delayed response task. The crows were instructed to plan an impending movement toward one of eight possible targets on the left or right side of a touchscreen. In a fraction of trials, the crows were prompted to plan a movement toward a self-chosen target. NCL neurons signaled the impending motion direction in instructed trials. Tuned neuronal activity during motor planning categorically represented the target side, but also specific target locations. As a marker of intentiona...

There is much debate about the existence and function of neural oscillatory mechanisms in the auditory system. The frequency-following response (FFR) is an index of neural periodicity encoding that can provide a vehicle to study entrainment in frequency ranges relevant to speech and music processing. Criteria for entrainment include the presence of poststimulus oscillations and phase alignment between stimulus and endogenous activity. To test the hypothesis of entrainment, in experiment 1 we collected FFR data for a repeated syllable using magnetoencephalography (MEG) and electroencephalography in 20 male and female human adults. We observed significant oscillatory activity after stimulus offset in auditory cortex and subcortical auditory nuclei, consistent with entrainment. In these structures, the FFR fundamental frequency converged from a lower value over 100 ms to the stimulus frequency, consistent with phase alignment, and diverged to a lower value after offset, consistent with relaxation to a preferr...