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...

This study compared the impact of spectral and temporal degradation on vocoded speech recognition between early-blind and sighted subjects. The participants included 25 early-blind subjects (30.32 ± 4.88 years; male:female, 14:11) and 25 age- and sex-matched sighted subjects. Tests included monosyllable recognition in noise at various signal-to-noise ratios (−18 to −4 dB), matrix sentence-in-noise recognition, and vocoded speech recognition with different numbers of channels (4, 8, 16, and 32) and temporal envelope cutoff frequencies (50 vs 500 Hz). Cortical-evoked potentials (N2 and P3b) were measured in response to spectrally and temporally degraded stimuli. The early-blind subjects displayed superior monosyllable and sentence recognition than sighted subjects (all p  < 0.01). In the vocoded speech recognition test, a three-way repeated-measure analysis of variance (two groups × four channels × two cutoff frequencies) revealed significant main effects of group, channel, and cutoff frequency (all p  < 0.0...

Forebrain neurons deprived of activity become hyperactive when activity is restored. Rebound activity has been linked to spontaneous seizures in vivo following prolonged activity blockade. Here, we measured the time course of rebound activity and the contributing circuit mechanisms using calcium imaging, synaptic staining, and whole-cell patch clamp in organotypic slice cultures of mouse neocortex. Calcium imaging revealed hypersynchronous activity increasing in intensity with longer periods of deprivation. While activity partially recovered 3 d after slices were released from 5 d of deprivation, they were less able to recover after 10 d of deprivation. However, even after the longer period of deprivation, activity patterns eventually returned to baseline levels. The degree of deprivation-induced rebound was age-dependent, with the greatest effects occurring when silencing began in the second week. Pharmacological blockade of NMDA receptors indicated that hypersynchronous rebound activity did not require a...

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...

Norepinephrine (NE), a neuromodulator released by locus ceruleus (LC) neurons throughout the cortex, influences arousal and learning through extrasynaptic vesicle exocytosis. While NE within cortical regions has been viewed as a homogenous field, recent studies have demonstrated heterogeneous axonal dynamics and advances in GPCR-based fluorescent sensors permit direct observation of the local dynamics of NE at cellular scale. To investigate how the spatiotemporal dynamics of NE release in the prefrontal cortex (PFC) affect neuronal firing, we employed in vivo two-photon imaging of layer 2/3 of the PFC in order to observe fine-scale neuronal calcium and NE dynamics concurrently. In this proof of principle study, we found that local and global NE fields can decouple from one another, providing a substrate for local NE spatiotemporal activity patterns. Optic flow analysis revealed putative release and reuptake events which can occur at the same location, albeit at different times, indicating the potential to ...

Retinal prosthetics are one of the leading therapeutic strategies to restore lost vision in patients with retinitis pigmentosa and age-related macular degeneration. Much work has described patterns of spiking in retinal ganglion cells (RGCs) in response to electrical stimulation, but less work has examined the underlying retinal circuitry that is activated by electrical stimulation to drive these responses. Surprisingly, little is known about the role of inhibition in generating electrical responses or how inhibition might be altered during degeneration. Using whole-cell voltage–clamp recordings during subretinal electrical stimulation in the rd10 and wild-type ( wt ) retina, we found electrically evoked synaptic inputs differed between ON and OFF RGC populations, with ON cells receiving mostly excitation and OFF cells receiving mostly inhibition and very little excitation. We found that the inhibition of OFF bipolar cells limits excitation in OFF RGCs, and a majority of both pre- and postsynaptic inhibiti...

Glutamatergic mossy cells (MCs) mediate associational and commissural connectivity, exhibiting significant heterogeneity along the septotemporal axis of the mouse dentate gyrus (DG). However, it remains unclear whether the neuronal features of MCs are conserved across mammals. This study compares the neuroanatomy of MCs in the DG of mice and monkeys. The MC marker, calretinin, distinguishes two subpopulations: septal and temporal. Dual-colored fluorescence labeling is utilized to compare the axonal projection patterns of these subpopulations. In both mice and monkeys, septal and temporal MCs project axons across the longitudinal axis of the ipsilateral DG, indicating conserved associational projections. However, unlike in mice, no MC subpopulations in monkeys make commissural projections to the contralateral DG. In monkeys, temporal MCs send associational fibers exclusively to the inner molecular layer, while septal MCs give rise to wide axonal projections spanning multiple molecular layers, akin to equiva...

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...

The Enhanced-Deep-Super-Resolution (EDSR) model is a state-of-the-art convolutional neural network suitable for improving image spatial resolution. It was previously trained with general-purpose pictures and then, in this work, tested on biomedical magnetic resonance (MR) images, comparing the network outcomes with traditional up-sampling techniques. We explored possible changes in the model response when different MR sequences were analyzed. T1w and T2w MR brain images of 70 human healthy subjects (F:M, 40:30) from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) repository were down-sampled and then up-sampled using EDSR model and BiCubic (BC) interpolation. Several reference metrics were used to quantitatively assess the performance of up-sampling operations (RMSE, pSNR, SSIM, and HFEN). Two-dimensional and three-dimensional reconstructions were evaluated. Different brain tissues were analyzed individually. The EDSR model was superior to BC interpolation on the selected metrics, both for two- ...

Seizures are generally associated with epilepsy but may also be a symptom of many other neurological conditions. A hallmark of a seizure is the intensity of the local neuronal activation, which can drive large-scale gene transcription changes. Such changes in the transcriptional profile likely alter neuronal function, thereby contributing to the pathological process. Therefore, there is a strong clinical imperative to characterize how gene expression is changed by seizure activity. To this end, we developed a simplified ex vivo technique for studying seizure-induced transcriptional changes. We compared the RNA sequencing profile in mouse neocortical tissue with up to 3 h of epileptiform activity induced by 4-aminopyridine (4AP) relative to control brain slices not exposed to the drug. We identified over 100 genes with significantly altered expression after 4AP treatment, including multiple genes involved in MAPK, TNF, and neuroinflammatory signaling pathways, all of which have been linked to epilepsy previ...