Dopaminergic (DA) neurons of the midbrain are involved in controlling orienting and approach of animals toward relevant external stimuli. The firing of DA neurons is regulated by many brain structures; however, the sensory input is provided predominantly by the ipsilateral superior colliculus (SC). It is suggested that SC also innervates the contralateral rostromedial tegmental nucleus (RMTg)—the main inhibitory input to DA neurons. Therefore, this study aimed to describe the physiology and anatomy of the SC–RMTg pathway. To investigate the anatomic connections within the circuit of interest, anterograde, retrograde, and transsynaptic tract-tracing studies were performed on male Sprague Dawley rats. We have observed that RMTg is monosynaptically innervated predominantly by the lateral parts of the intermediate layer of the contralateral SC. To study the physiology of this neuronal pathway, we conducted in vivo electrophysiological experiments combined with optogenetics; the activity of RMTg neurons was rec...

The development of the human brain continues through to early adulthood. It has been suggested that cortical plasticity during this protracted period of development shapes circuits in associative transmodal regions of the brain. Here we considered how cortical plasticity during development might contribute to the coordinated brain activity required for speech motor learning. Specifically, we examined patterns of brain functional connectivity (FC), whose strength covaried with the capacity for speech audio-motor adaptation in children ages 5–12 and in young adults of both sexes. Children and adults showed distinct patterns of the encoding of learning in the brain. Adult performance was associated with connectivity in transmodal regions that integrate auditory and somatosensory information, whereas children rely on basic somatosensory and motor circuits. A progressive reliance on transmodal regions is consistent with human cortical development and suggests that human speech motor adaptation abilities are bui...

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...

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...

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...

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...

The central noradrenergic (NA) system is critical for maintenance of attention, behavioral flexibility, spatial navigation, and learning and memory, those cognitive functions lost first in early Alzheimer’s disease (AD). In fact, the locus coeruleus (LC), the sole source of norepinephrine (NE) for >90% of the brain, is the first site of pathological tau accumulation in human AD with axon loss throughout forebrain, including hippocampus. The dentate gyrus (DG) is heavily innervated by LC-NA axons, where released norepinephrine (NE) acts on β-adrenergic receptors (ARs) at excitatory synapses from entorhinal cortex (EC) to facilitate long-term synaptic plasticity and memory formation. These synapses dysfunction in early AD prior to cognitive impairment. In the TgF344-AD rat model of AD, degeneration of LC-NA axons in hippocampus recapitulates human AD, providing a preclinical model to investigate synaptic and behavioral consequences. Using immunohistochemistry, Western blot analysis, and brain slice electroph...