Canonically, action potentials of most mammalian neurons initiate at the axon initial segment (AIS) and propagate bidirectionally: orthodromically along the distal axon and retrogradely into the soma and dendrites. Under some circumstances, action potentials may initiate ectopically, at sites distal to the AIS, and propagate antidromically along the axon. These “ectopic action potentials” (EAPs) have been observed in experimental models of seizures and chronic pain, and more rarely in nonpathological forebrain neurons. Here we report that a large majority of parvalbumin-expressing (PV+) interneurons in the upper layers of mouse neocortex, from both orbitofrontal and primary somatosensory areas, fire EAPs after sufficient activation of their somata. Somatostatin-expressing interneurons also fire EAPs, though less robustly. Ectopic firing in PV+ cells occurs in varying temporal patterns and can persist for several seconds. PV+ cells evoke strong synaptic inhibition in pyramidal neurons and interneurons and p...

Sleep spindles appear to play an important role in learning new motor skills. Motor skill learning engages several brain regions with two important areas being the motor cortex (M1) and the cerebellum (CB). However, the neurophysiological processes in these areas during sleep, especially how spindle oscillations affect local and cross-region spiking, are not fully understood. We recorded an activity from the M1 and cerebellar cortex in eight rats during spontaneous activity to investigate how sleep spindles in these regions are related to local spiking as well as cross-region spiking. We found that M1 firing was significantly changed during both M1 and CB spindles, and this spiking occurred at a preferred phase of the spindle. On average, M1 and CB neurons showed most spiking at the M1 or CB spindle peaks. These neurons also developed a preferential phase locking to local or cross-area spindles with the greatest phase-locking value at spindle peaks; however, this preferential phase locking was not signific...

Emotionally salient components of memory are preferentially remembered at the expense of accompanying neutral information. This emotional memory trade-off is enhanced over time, and possibly sleep, through a process of memory consolidation. Sleep is believed to benefit memory through a process of reactivation during nonrapid eye movement sleep (NREM). Here, targeted memory reactivation (TMR) was used to manipulate the reactivation of negative and neutral memories during NREM sleep. Thirty-one male and female participants encoded composite scenes containing either a negative or neutral object superimposed on an always neutral background. During NREM sleep, sounds associated with the scene object were replayed, and memory for object and background components was tested the following morning. We found that TMR during NREM sleep improved memory for neutral, but not negative scene objects. This effect was associated with sleep spindle activity, with a larger spindle response following TMR cues predicting TMR ef...

What factors are associated with career outcomes among biomedical PhDs? Research to date has focused on drivers of interest in (and intention to pursue) various careers, especially during graduate school, but fewer studies have investigated participants’ ultimate career outcomes. Even less is known about what factors matter for groups historically underrepresented in the US science, technology, engineering, and mathematics (STEM) workforce, such as women, some racial and ethnic groups, and persons with disabilities ( [National Center for Science and Engineering Statistics (NCSES), 2021a][1]). This study reports a new analysis of data from 781 PhD neuroscientists that were obtained from a retrospective survey ( [Ullrich et al., 2021][2]) to investigate the factors that influence the career sector in which neuroscience PhDs are employed and whether there were group differences according to social identity. We find evidence of academia as a “default path” for incoming PhD students, but interest in different c...

In the article, “Context Binding in Visual Working Memory Is Reflected in Bilateral Event-Related Potentials, But Not in Contralateral Delay Activity,” by Ying Cai, Jacqueline M. Fulvio, Jason Samaha, …

The voltage-gated calcium channel subunit α2δ-2 controls calcium-dependent signaling in neurons, and loss of this subunit causes epilepsy in both mice and humans. To determine whether mice without α2δ-2 demonstrate hippocampal activation or histopathological changes associated with seizure activity, we measured expression of the activity-dependent gene c -fos and various histopathological correlates of temporal lobe epilepsy (TLE) in hippocampal tissue from wild-type (WT) and α2δ-2 knock-out ( CACNA2D2 KO) mice using immunohistochemical staining and confocal microscopy. Both genotypes demonstrated similarly sparse c- fos and ΔFosB expressions within the hippocampal dentate granule cell layer (GCL) at baseline, consistent with no difference in basal activity of granule cells between genotypes. Surprisingly, when mice were assayed 1 h after handling-associated convulsions, KO mice had fewer c- fos -positive cells but dramatically increased ΔFosB expression in the dentate gyrus compared with WT mice. After ad...

A hallmark of Parkinson's disease is the appearance of correlated oscillatory discharge throughout the cortico-basal ganglia (BG) circuits. In the primate globus pallidus (GP), where the discharge of GP neurons is normally uncorrelated, pairs of GP neurons exhibit oscillatory spike correlations with a broad distribution of pairwise phase delays in experimental parkinsonism. The transition to oscillatory correlations is thought to indicate the collapse of the normally segregated information channels traversing the BG. The large phase delays are thought to reflect pathological changes in synaptic connectivity in the BG. Here we study the structure and phase delays of spike correlations measured from neurons in the mouse external GP (GPe) subjected to identical 1–100 Hz sinusoidal drive but recorded in separate experiments. First, we found that spectral modes of a GPe neuron's empirical instantaneous phase response curve (iPRC) elucidate at what phases of the oscillatory drive the GPe neuron locks when it is ...

Why does groundbreaking progress in our understanding of the brain seem scarce (at least to me)? The prevailing system of research funding and publication, deeply rooted in peer review and contingent upon preliminary data, tends to favor safe, conventional ideas, thereby impeding major breakthroughs. The prerequisite of preliminary data for hypothesis validation transforms grant-seeking into a cycle that prioritizes data accumulation over pioneering ideas, fostering publications that align with pre-established notions endorsed by reviewers. Are we, the scientists, becoming akin to the subjects of our experiments? Consider this: in behavioral studies, rodents are often deprived of food and water to motivate their learning of a task. Since a successful task is rewarded, animals quickly learn the task and become very efficient at it after some time. Now, envision neuroscientists in a similar plight, navigating the pursuit of funding and recognition in high-profile journals. This predicament is faced by many (...

Singing-based treatments of aphasia can improve language outcomes, but the neural benefits of group-based singing in aphasia are unknown. Here, we set out to determine the structural neuroplasticity changes underpinning group-based singing-induced treatment effects in chronic aphasia. Twenty-eight patients with at least mild nonfluent poststroke aphasia were randomized into two groups that received a 4-month multicomponent singing intervention (singing group) or standard care (control group). High-resolution T1 images and multishell diffusion-weighted MRI data were collected in two time points (baseline/5 months). Structural gray matter (GM) and white matter (WM) neuroplasticity changes were assessed using language network region of interest-based voxel-based morphometry (VBM) and quantitative anisotropy-based connectometry, and their associations to improved language outcomes (Western Aphasia Battery Naming and Repetition) were evaluated. Connectometry analyses showed that the singing group enhanced struc...

Historically, the orbitofrontal cortex (OFC) has been implicated in a variety of behaviors ranging from reversal learning and inhibitory control to more complex representations of reward value and task space. While modern interpretations of the OFC's function have focused on a role in outcome evaluation, these cognitive processes often require an organism to inhibit a maladaptive response or strategy. Single-unit recordings from the OFC in rats performing a stop-change task show that the OFC responds strongly to STOP trials. To investigate the role that the OFC plays in stop-change performance, we expressed halorhodopsin (eNpHR3.0) in excitatory neurons in the OFC and tested rats on the stop-change task. Previous work suggests that the OFC differentiates between STOP trials based on trial sequence (i.e., gS trials: STOP trials preceded by a GO vs sS trials: STOP trials preceded by a STOP). We found that yellow light activation of the eNpHR3.0-expressing neurons significantly decreased accuracy only on STOP...