In similar states, neural circuits produce similar outputs across individuals despite substantial interindividual variability in neuronal ionic conductances and synapses. Circuit states are largely shaped by neuromodulators that tune ionic conductances. It is therefore possible that, in addition to producing flexible circuit output, neuromodulators also contribute to output similarity despite varying ion channel expression. We studied whether neuromodulation at saturating concentrations can increase the output similarity of a single identified neuron across individual animals. Using the lateral pyloric (LP) neuron of the crab stomatogastric ganglion, we compared the variability of f–I (frequency–current) curves and rebound properties in the presence of neuropeptides. The two neuropeptides we used converge to activate the same target current, which increases neuronal excitability. Output variability was lower in the presence of the neuropeptides, regardless of whether the neuropeptides significantly changed...

Typical everyday sounds, such as those of speech or running water, are spectrotemporally complex. The ability to recognize complex sounds (CxSs) and their associated meaning is presumed to rely on their stable neural representations across time. The auditory cortex is critical for the processing of CxSs, yet little is known of the degree of stability of auditory cortical representations of CxSs across days. Previous studies have shown that the auditory cortex represents CxS identity with a substantial degree of invariance to basic sound attributes such as frequency. We therefore hypothesized that auditory cortical representations of CxSs are more stable across days than those of sounds that lack spectrotemporal structure such as pure tones (PTs). To test this hypothesis, we recorded responses of identified layer 2/3 auditory cortical excitatory neurons to both PTs and CxSs across days using two-photon calcium imaging in awake mice. Auditory cortical neurons showed significant daily changes of responses to ...

Opioid misuse among pregnant women is rapidly increasing in the United States. The number of maternal opioid-related diagnoses increased by 131% in the last 10 years, resulting in an increased number of infants exposed to opioids in utero and a subsequent increase in infants developing neonatal abstinence syndrome (NAS). The most prescribed treatment to combat maternal opioid use disorder is buprenorphine, a partial μ-opioid receptor agonist and κ-opioid receptor antagonist. Buprenorphine treatment effectively reduces NAS but has been associated with disrupted cortical development and neurodevelopmental consequences in childhood. Less is known about the long-term neurodevelopmental consequences following buprenorphine exposure in utero . Previous research has shown that gestational buprenorphine exposure can induce anxiety-like and depressive-like phenotypes in adult rats, suggesting that exposure to buprenorphine in utero may render individuals more susceptible to psychiatric illness in adulthood. A commo...

Drinking behavior has been used in fundamental research to study metabolism, motivation, decision-making and different aspects of health problems, such as anhedonia and alcohol use disorders. In the majority of studies, liquid intake is measured by weighing the bottles before and after the experiment. This method does not tell much about the drinking microstructure, e.g., licking bouts and periods of preference for each liquid, which could be valuable to understand drinking behavior. To improve data acquisition of drinking microstructure, companies have developed lickometer devices that acquire timestamps when animals approach or drink from a specific sipper. Nevertheless, commercially available devices have elevated costs. Here, we present a low-cost alternative for a lickometer system that allows wireless data acquisition of licks from eight cages with two sippers each. We ran a three-phase validation protocol to ensure (1) proper choice of the sensor to detect licks; (2) adaptation of the device to a wi...

After unilateral lesion of the medial forebrain bundle by 6-OHDA rats exhibit lateralized deficits in spontaneous behavior or apomorphine-induced rotations. We investigated whether such lateralization is attenuated by either deep brain stimulation (DBS) or glutamatergic neurotransmission in the inferior colliculus (IC) of Wistar rats. Intracollicular DBS did not affect spontaneous lateralization but attenuated apomorphine-induced rotations. Spontaneous lateralization disappeared after either the glutamatergic antagonist MK-801 or the agonist NMDA microinjections into the IC. Apomorphine-induced rotations were potentiated by MK-801 but were not affected by NMDA intracollicular microinjection. After injecting a bidirectional neural tract tracer into the IC, cell bodies and/or axonal fibers were found in the periaqueductal gray matter, superior colliculus, substantia nigra, cuneiform nucleus, and pedunculo-pontine tegmental nucleus, suggesting the involvement of these structures in the motor improvement after...

In the article “Evidence for Paracrine Protective Role of Exogenous αA-Crystallin in Retinal Ganglion Cells,” by Madhu Nath, Zachary B. Sluzala, Ashutosh S. Phadte, Yang Shan, Angela …

CRISPR/Cas9-mediated knock-in methods enable the labeling of individual endogenous proteins to faithfully determine their spatiotemporal distribution in cells. However, reliable multiplexing of knock-in events in neurons remains challenging because of cross talk between editing events. To overcome this, we developed conditional activation of knock-in expression (CAKE), allowing efficient, flexible, and accurate multiplex genome editing. To diminish cross talk, CAKE is based on sequential, recombinase-driven guide RNA (gRNA) expression to control the timing of genomic integration of each donor sequence. We show that CAKE is broadly applicable in rat neurons to co-label various endogenous proteins, including cytoskeletal proteins, synaptic scaffolds, ion channels and neurotransmitter receptor subunits. To take full advantage of CAKE, we resolved the nanoscale co-distribution of endogenous synaptic proteins using super-resolution microscopy, demonstrating that their co-organization correlates with synapse siz...

Before visual information from the retina reaches primary visual cortex (V1), it is dynamically filtered by the lateral geniculate nucleus (LGN) of the thalamus, the first location within the visual hierarchy at which nonretinal structures can significantly influence visual processing. To explore the form and dynamics of geniculate filtering we used data from monosynpatically connected pairs of retinal ganglion cells (RGCs) and LGN relay cells in the cat that, under anesthetized conditions, were stimulated with binary white noise and/or drifting sine-wave gratings to train models of increasing complexity to predict which RGC spikes were relayed to cortex, what we call “relay status.” In addition, we analyze and compare a smaller dataset recorded in the awake state to assess how anesthesia might influence our results. Consistent with previous work, we find that the preceding retinal interspike interval (ISI) is the primary determinate of relay status with only modest contributions from longer patterns of re...

Spreading depolarization (SD) is a slow-moving wave of neuronal depolarization accompanied by a breakdown of ion concentration homeostasis, followed by long periods of neuronal silence (spreading depression), and is associated with several neurologic conditions. We developed multiscale (ions to tissue slice) computer models of SD in brain slices using the NEURON simulator: 36,000 neurons (two voltage-gated ion channels; three leak channels; three ion exchangers/pumps) in the extracellular space (ECS) of a slice (1 mm sides, varying thicknesses) with ion (K+, Cl–, Na+) and O2 diffusion and equilibration with a surrounding bath. Glia and neurons cleared K+ from the ECS via Na+/K+ pumps. SD propagated through the slices at realistic speeds of 2–4 mm/min, which increased by as much as 50% in models incorporating the effects of hypoxia or propionate. In both cases, the speedup was mediated principally by ECS shrinkage. Our model allows us to make testable predictions, including the following: (1) SD can be inhi...

Neural responses of dorsal visual area V7 and lateral occipital complex (LOC) have been shown to correlate with changes in behavioral metrics of depth sensitivity observed as a function of object context, although it is unclear as to whether the behavioral manifestation results from an alteration of early depth-specific responses in V7 or arises as a result of alterations of object-level representations at LOC that subsequently feed back to affect disparity readouts in dorsal cortex. Here, we used online transcranial magnetic stimulation (TMS) to examine the roles of these two areas in giving rise to context–disparity interactions. Stimuli were disparity-defined geometric objects rendered as random-dot stereograms, presented in geometrically plausible and implausible variations. Observers’ sensitivity to depth (depth discrimination) or object identity (plausibility discrimination) was indexed while receiving repetitive TMS at one of the two sites of interest (V7, LOC) along with a control site (Cz). TMS ov...