Reverberation is ubiquitous in everyday acoustic environments. It degrades both binaural cues and the envelope modulations of sounds and thus can impair speech perception. Still, both humans and animals can accurately perceive reverberant stimuli in most everyday settings. Previous neurophysiological and perceptual studies have suggested the existence of neural mechanisms that partially compensate for the effects of reverberation. However, these studies were limited by their use of either highly simplified stimuli or rudimentary reverberation simulations. To further characterize how reverberant stimuli are processed by the auditory system, we recorded single-unit (SU) and multiunit (MU) activity from the inferior colliculus (IC) of unanesthetized rabbits in response to natural speech utterances presented with no reverberation (“dry”) and in various degrees of simulated reverberation (direct-to-reverberant energy ratios (DRRs) ranging from 9.4 to –8.2 dB). Linear stimulus reconstruction techniques ([Mesgara...

PyMouseTracks (PMT) is a scalable and customizable computer vision and radio frequency identification (RFID)-based system for multiple rodent tracking and behavior assessment that can be set up within minutes in any user-defined arena at minimal cost. PMT is composed of the online Raspberry Pi (RPi)-based video and RFID acquisition with subsequent offline analysis tools. The system is capable of tracking up to six mice in experiments ranging from minutes to days. PMT maintained a minimum of 88% detections tracked with an overall accuracy >85% when compared with manual validation of videos containing one to four mice in a modified home-cage. As expected, chronic recording in home-cage revealed diurnal activity patterns. In open-field, it was observed that novel noncagemate mouse pairs exhibit more similarity in travel trajectory patterns than cagemate pairs over a 10-min period. Therefore, shared features within travel trajectories between animals may be a measure of sociability that has not been previously...

Therapeutic hypothermia is well established as a standard treatment for infants with hypoxic-ischemic (HI) encephalopathy but it is only partially effective. The potential for combination treatments to augment hypothermic neuroprotection has major relevance. Our aim was to assess the effects of treating newborn rats following HI injury with cannabidiol (CBD) at 0.1 or 1 mg/kg, i.p., in normothermic (37.5°C) and hypothermic (32.0°C) conditions, from 7 d of age (neonatal phase) to 37 d of age (juvenile phase). Placebo or CBD was administered at 0.5, 24, and 48 h after HI injury. Two sensorimotor (rotarod and cylinder rearing) and two cognitive (novel object recognition and T-maze) tests were conducted 30 d after HI. The extent of brain damage was determined by magnetic resonance imaging, histologic evaluation, magnetic resonance spectroscopy, amplitude-integrated electroencephalography, and Western blotting. At 37 d, the HI insult produced impairments in all neurobehavioral scores (cognitive and sensorimotor...

Glaucoma is a neurodegenerative condition in which increased intraocular pressure (IOP) causes progressive degeneration of retinal ganglion cells (RGCs), the neurons projecting from the retina to secondary visual areas of the brain. Raised IOP results in apoptosis of RGCs because of damage to RGC axons at the optic nerve head. Axonal damage triggers disruption of RGC mitochondria, metabolism, and active transport. It also disturbs the anatomic distribution of excitatory connections in RGC targets, including the superior colliculus and the thalamic dorsal lateral geniculate nucleus (dLGN). However, the timeline of the processes linking initial damage to RGC death is not well characterized. It is especially unclear at which point functional changes begin in excitatory synapses between RGCs and target structures like the thalamocortical (TC) neurons in the dLGN. To solve this conundrum, Smith et al. (2022) established a timeline for the pathologic processes induced by raised IOP by studying the RGC to TC syna...

The accumulation of α-synuclein (α-syn)-enriched protein aggregates is thought to arise from dysfunction in degradation systems within the brain. Recently, missense mutations of SYNJ1 encoding the SAC1 and 5’-phosphatase domains have been found in families with hereditary early-onset Parkinsonism. Previous studies showed that Synj1 haploinsufficiency ( Synj1 +/−) leads to accumulation of the autophagy substrate p62 and pathologic α-syn proteins in the midbrain (MB) and striatum of aged mice. In this study, we aim to investigate the neuronal degradation pathway using the Synj1 +/− MB culture from mouse pups of mixed sex as a model. Our data show that GFP-LC3 puncta formation and cumulative mKeima puncta formation are unaltered at baseline in Synj1 +/− MB neurons. However, GFP-LAMP1 puncta is reduced with a similar decrease in endogenous proteins, including lysosomal-associated membrane protein (LAMP)1, LAMP2, and LAMP2A. The LAMP1 vesicles are hyperacidified with enhanced enzymatic activity in Synj1 +/− MB ...

Brain-derived neurotrophic factor (BDNF) is released from axon terminals originating in the cerebral cortex onto striatal neurons. Here, we characterized BDNF neurons in the corticostriatal circuitry. First, we used BDNF -Cre and Ribotag transgenic mouse lines to label BDNF-positive neurons in the cortex and detected BDNF expression in all the subregions of the prefrontal cortex (PFC). Next, we used a retrograde viral tracing strategy, in combination with BDNF -Cre knock-in mice, to map the cortical outputs of BDNF neurons in the dorsomedial and dorsolateral striatum (DMS and DLS, respectively). We found that BDNF- expressing neurons located in the medial prefrontal cortex (mPFC) project mainly to the DMS, and those located in the primary and secondary motor cortices (M1 and M2, respectively) and agranular insular cortex (AI) project mainly to the DLS. In contrast, BDNF- expressing orbitofrontal cortical (OFC) neurons differentially target the dorsal striatum (DS) depending on their mediolateral and rostro...

Encoding and processing sensory information is key to understanding the environment and to guiding behavior accordingly. Characterizing the behavioral and neural correlates of these processes requires the experimenter to have a high degree of control over stimuli presentation. For auditory stimulation in animals with relatively large heads, this can be accomplished by using headphones. However, it has proven more challenging in smaller species, such as rats and mice, and has been only partially solved using closed-field speakers in anesthetized or head-restrained preparations. To overcome the limitations of such preparations and to deliver sound with high precision to freely moving animals, we have developed a set of miniature headphones for rats. The headphones consist of a small, skull-implantable base attached with magnets to a fully adjustable structure that holds the speakers and keeps them in the same position with respect to the ears.

Mesolimbic nicotinic acetylcholine receptor (nAChRs) activation is necessary for nicotine reinforcement behavior, but it is unknown whether selective activation of nAChRs in the dopamine (DA) reward pathway is sufficient to support nicotine reinforcement. In this study, we tested the hypothesis that activation of β2-containing (β2*) nAChRs on VTA neurons is sufficient for intravenous nicotine self-administration (SA). We expressed β2 nAChR subunits with enhanced sensitivity to nicotine (referred to as β2Leu9′Ser) in the VTA of male Sprague Dawley (SD) rats, enabling very low concentrations of nicotine to selectively activate β2* nAChRs on transduced neurons. Rats expressing β2Leu9′Ser subunits acquired nicotine SA at 1.5 μg/kg/infusion, a dose too low to support acquisition in control rats. Saline substitution extinguished responding for 1.5 μg/kg/inf, verifying that this dose was reinforcing. β2Leu9′Ser nAChRs also supported acquisition at the typical training dose in rats (30 μg/kg/inf) and reducing the ...

Spinal cord stimulation (SCS) evokes fast epidural Evoked Compound Action Potential (ECAPs) that represent activity of dorsal column axons, but not necessarily a spinal circuit response. Using a multimodal approach, we identified and characterized a delayed and slower potential evoked by SCS that reflects synaptic activity within the spinal cord. Anesthetized female Sprague Dawley rats were implanted with an epidural SCS lead, epidural motor cortex stimulation electrodes, an epidural spinal cord recording lead, an intraspinal penetrating recording electrode array, and intramuscular electromyography (EMG) electrodes in the hindlimb and trunk. We stimulated the motor cortex or the epidural spinal cord and recorded epidural, intraspinal, and EMG responses. SCS pulses produced characteristic propagating ECAPs (composed of P1, N1, and P2 waves with latencies <2 ms) and an additional wave (“S1”) starting after the N2. We verified the S1-wave was not a stimulation artifact and was not a reflection of hindlimb/tru...

Autism spectrum disorder (ASD) is a common neurodevelopmental condition for which there are no pharmacological therapies that effectively target its core symptomatology. Animal models of syndromic forms of ASD, such as neurofibromatosis type 1, may be of use in screening for such treatments. Drosophila larvae lacking Nf1 expression exhibit tactile hypersensitivity following mechanical stimulation, proposed to mirror the sensory sensitivity issues comprising part of the ASD diagnostic criteria. Such behavior is associated with synaptic dysfunction at the neuromuscular junction (NMJ). Both phenotypes may thus provide tractable outputs with which to screen for potential ASD therapies. In this study, we demonstrate that, while loss of Nf1 expression within the embryo is sufficient to impair NMJ synaptic transmission in the larva, constitutive Nf1 knockdown is required to induce tactile hypersensitivity, suggesting that a compound must be administered throughout development to rescue this behavior. With such a ...