Loss of olfactory sensory neurons (OSNs) after injury to the olfactory epithelium (OE) triggers the generation of OSNs that are incorporated into olfactory circuits to restore olfactory sensory perception. This study addresses how insulin receptor-mediated signaling affects the functional recovery of OSNs after OE injury. Insulin levels were reduced in mice by ablating the pancreatic β cells via streptozotocin (STZ) injections. These STZ-induced diabetic and control mice were then intraperitoneally injected with the olfactotoxic drug methimazole to selectively ablate OSNs. The OE of diabetic and control mice regenerated similarly until day 14 after injury. Thereafter, the OE of diabetic mice contained fewer mature and more apoptotic OSNs than control mice. Functionally, diabetic mice showed reduced electro-olfactogram (EOG) responses and their olfactory bulbs (OBs) had fewer c-Fos-active cells following odor stimulation, as well as performed worse in an odor-guided task compared with control mice. Insulin ...

Operant behavior procedures often rely on visual stimuli to cue the initiation or secession of a response, and to provide a means for discriminating between two or more simultaneously available responses. While primate and human studies typically use Liquid-Crystal Display (LCD) or Organic Light-Emitting Diode (OLED) monitors and touch screens, rodent studies use a variety of methods to present visual cues ranging from traditional incandescent light bulbs, single LEDs, and, more recently, touch screen monitors. Commercially available systems for visual stimulus presentation are costly, challenging to customize, and are typically closed source. We developed an open-source, highly-modifiable visual stimulus presentation platform that can be combined with a 3D-printed operant response device. The device uses an 8 × 8 matrix of LEDs, and can be expanded to control much larger LED matrices. Implementing the platform is low-cost (<$70 USD per device in the year 2020). Using the platform, we trained rats to make ...

In humans, finely tuned γ synchronization (60–90 Hz) rapidly appears at movement onset in a motor control network involving primary motor cortex, the basal ganglia and motor thalamus. Yet the functional consequences of brief movement-related synchronization are still unclear. Distinct synchronization phenomena have also been linked to different forms of motor inhibition, including relaxing antagonist muscles, rapid movement interruption and stabilizing network dynamics for sustained contractions. Here, I will introduce detailed hypotheses about how intrasite and intersite synchronization could interact with firing rate changes in different parts of the network to enable flexible action control. The here proposed cause-and-effect relationships shine a spotlight on potential key mechanisms of cortico-basal ganglia-thalamo-cortical (CBGTC) communication. Confirming or revising these hypotheses will be critical in understanding the neuronal basis of flexible movement initiation, invigoration and inhibition. Ul...

The “habenulopeduncular system” consists of the medial habenula (MHb) and its principal target of innervation, the interpeduncular nucleus (IP). Neurons in the ventral MHb (MHbV) express acetylcholine along with glutamate, and both the MHb and IP are rich in nicotinic acetylcholine receptors. Much of the work on this system has focused on nicotinic mechanisms and their clinical implications for nicotine use, particularly because the IP expresses the α5 nicotinic receptor subunit, encoded by the CHRNA5 gene, which is genetically linked to smoking risk. A working model has emerged in which nicotine use may be determined by the balance of reinforcement mediated in part by nicotine effects on dopamine reward pathways, and an aversive “brake” on nicotine consumption encoded in the MHb-IP pathway. However, recent work has proposed that the IP also receives direct dopaminergic input from the ventral tegmental area (VTA). If correct, this would significantly impact the prevailing model of IP function. Here, we hav...

Super-resolution microscopy provides valuable insight for understanding the nanoscale organization within living tissue, although this method is typically restricted to cultured or dissociated cells. Here, we develop a method to track the mobility of individual proteins in ex vivo adult Drosophila melanogaster brains, focusing on a key component of the presynaptic release machinery, syntaxin1A (Sx1a). We show that individual Sx1a dynamics can be reliably tracked within neurons in the whole fly brain, and that the mobility of Sx1a molecules increases following conditional neural stimulation. We then apply this preparation to the problem of general anesthesia, to address how different anesthetics might affect single molecule dynamics in intact brain synapses. We find that propofol, etomidate, and isoflurane significantly impair Sx1a mobility, while ketamine and sevoflurane have little effect. Resolving single molecule dynamics in intact fly brains provides a novel approach to link localized molecular effects...

Diverse gene products contribute to the pathogenesis of Alzheimer’s disease (AD). Experimental models have helped elucidate their mechanisms and impact on brain functions. Human amyloid precursor protein (hAPP) transgenic mice from line J20 (hAPP-J20 mice) are widely used to simulate key aspects of AD. However, they also carry an insertional mutation in noncoding sequence of one Zbtb20 allele, a gene involved in neural development. We demonstrate that heterozygous hAPP-J20 mice have reduced Zbtb20 expression in some AD-relevant brain regions, but not others, and that Zbtb20 levels are higher in hAPP-J20 mice than heterozygous Zbtb20 knock-out ( Zbtb20 +/–) mice. Whereas hAPP-J20 mice have premature mortality, severe deficits in learning and memory, other behavioral alterations, and prominent nonconvulsive epileptiform activity, Zbtb20 +/– mice do not. Thus, the insertional mutation in hAPP-J20 mice does not ablate the affected Zbtb20 allele and is unlikely to account for the AD-like phenotype of this model.

Although moving sound-sources abound in natural auditory scenes, it is not clear how the human brain processes auditory motion. Previous studies have indicated that, although ocular localization responses to stationary sounds are quite accurate, ocular smooth pursuit of moving sounds is very poor. We here demonstrate that human subjects faithfully track a sound’s unpredictable movements in the horizontal plane with smooth-pursuit responses of the head. Our analysis revealed that the stimulus–response relation was well described by an under-damped passive, second-order low-pass filter in series with an idiosyncratic, fixed, pure delay. The model contained only two free parameters: the system’s damping coefficient, and its central (resonance) frequency. We found that the latter remained constant at ∼0.6 Hz throughout the experiment for all subjects. Interestingly, the damping coefficient systematically increased with trial number, suggesting the presence of an adaptive mechanism in the auditory pursuit syste...

Voices are arguably among the most relevant sounds in humans’ everyday life, and several studies have suggested the existence of voice-selective regions in the human brain. Despite two decades of research, defining the human brain regions supporting voice recognition remains challenging. Moreover, whether neural selectivity to voices is merely driven by acoustic properties specific to human voices (e.g., spectrogram, harmonicity), or whether it also reflects a higher-level categorization response is still under debate. Here, we objectively measured rapid automatic categorization responses to human voices with fast periodic auditory stimulation (FPAS) combined with electroencephalography (EEG). Participants were tested with stimulation sequences containing heterogeneous non-vocal sounds from different categories presented at 4 Hz (i.e., four stimuli/s), with vocal sounds appearing every three stimuli (1.333 Hz). A few minutes of stimulation are sufficient to elicit robust 1.333 Hz voice-selective focal brai...

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. Neurologic 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 neurologic disorders. In this way, the zebrafish ( Danio rerio ) organism model represents an attractive tool in the field of neuroscience, showing economic and logistic advantages besides genetic and physiologic similarities with mammalian, including the brain structure and functions. Besides, its external embryonic development, high avail...

The marmoset has emerged as a promising primate model system, in particular for visual neuroscience. Many common experimental paradigms rely on head fixation and an extended period of eye fixation during the presentation of salient visual stimuli. Both of these behavioral requirements can be challenging for marmosets. Here, we present two methodological developments, each addressing one of these difficulties. First, we show that it is possible to use a standard eye-tracking system without head fixation to assess visual behavior in the marmoset. Eye-tracking quality from head-free animals is sufficient to obtain precise psychometric functions from a visual acuity task. Second, we introduce a novel method for efficient receptive field (RF) mapping that does not rely on moving stimuli but uses fast flashing annuli and wedges. We present data recorded during head-fixation in areas V1 and V6 and show that RF locations are readily obtained within a short period of recording time. Thus, the methodological advance...