In the article “Differential Electrographic Signatures Generated by Mechanistically-Diverse Seizurogenic Compounds in the Larval Zebrafish Brain,” by Joseph Pinion, Callum Walsh, Marc Goodfellow, …

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...

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...

A hallmark of human reaching movements is that they are appropriately tuned to the task goal and to the environmental context. This was demonstrated by the way humans flexibly respond to mechanical and visual perturbations that happen during movement. Furthermore, it was previously showed that the properties of goal-directed control can change within a movement, following abrupt changes in the goal structure. Such online adjustment was characterized by a modulation of feedback gains following switches in target shape. However, it remains unknown whether the underlying mechanism merely switches between prespecified policies, or whether it results from continuous and potentially dynamic adjustments. Here, we address this question by investigating participants’ feedback control strategies in presence of various changes in target width during reaching. More specifically, we studied whether the feedback responses to mechanical perturbations were sensitive to the rate of change in target width, which would be in...

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...

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...

As readers of eNeuro , we would agree that neurons are important cells—you are using them right now to read and understand this article [unless you are a sentient AI (artificial intelligence)–LaMDA (Language Model for Dialogue Applications); I would love to be friends!]. There are still a lot of unknowns about how neuronal proteins contribute to neuronal function. What exactly are the proteins in your neurons doing as you are reading this? We may not be able to determine that yet, but being able to visualize proteins in living neurons in culture is an important step toward that goal. The benefit of being able to “see” proteins is that you can determine where they go and how they move around in living cells. You can also get an idea of which proteins are interacting with each other. Fluorescent labeling of proteins has proven to be a useful tool for visualizing proteins in living cells. Historically, though, this method has had its drawbacks. In order to add a fluorescent tag to a protein, a gene encoding ...

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 …

Arginine vasopressin (AVP) serves as a neuromodulator in the brain. The hippocampus is one of the major targets for AVP as has been demonstrated that the hippocampus receives vasopressinergic innervation and expresses AVP receptors. The dentate gyrus (DG) granule cells (GCs) serve as a gate governing the inflow of information to the hippocampus. High densities of AVP receptors are expressed in the DG GCs. However, the roles and the underlying cellular and molecular mechanisms of AVP in the DG GCs have not been determined. We addressed this question by recording from the DG GCs in rat hippocampal slices. Our results showed that application of AVP concentration-dependently evoked an inward holding current recorded from the DG GCs. AVP depolarized the DG GCs and increased their action potential firing frequency. The excitatory effects of AVP were mediated by activation of V1a receptors and required the function of phospholipase Cβ (PLCβ). Whereas intracellular Ca2+ release and protein kinase C (PKC) activity ...

Foraging entails a complex balance between approach and avoidance alongside sensorimotor and homeostatic processes under the control of multiple cortical and subcortical areas. Recently, it has become clear that several thalamic nuclei located near the midline regulate motivated behaviors. However, one midline thalamic nucleus that project to key nodes in the foraging network, the central medial (CMT) nucleus, has received little attention so far. Therefore, the present study examined CMT contributions to foraging behavior using inactivation and unit recording techniques in male rats. Inactivation of CMT or the basolateral amygdala (BLA) with muscimol abolished the rats’ normally cautious behavior in the foraging task. Moreover, CMT neurons showed large but heterogeneous activity changes during the foraging task, with many neurons decreasing or increasing their discharge rates, with a modest bias for the latter. A generalized linear model revealed that the nature (inhibitory vs. excitatory) and relative ma...