Forming a long-term memory requires changes in neuronal transcription. What happens, though, as the memory is forgotten? And how does the transcriptional state relate to the maintenance and recall of the long-term memory? To answer these questions, we have been systematically tracing the time course of transcriptional changes evoked by long-term sensitization in the marine mollusk Aplysia californica . Our approach captures transcriptional changes in neurons of known behavioral relevance using a within-subject design, delineating patterns of transcriptional change that are comprehensive and reproducible. We have previously reported that within 1 d of long-term sensitization training, there is a widespread transcriptional response involving robust changes in over 5% of tested transcripts (1,198 of ∼22 k; [Conte et al., 2017][1]). Within 1 week, however, memory strength fades, and nearly all transcriptional changes relapse to baseline ( [Perez et al., 2018][2]). Here we report microarray analysis ( N  = 16) ...

A possible mechanism of temporal lobe epilepsy is insufficient inhibition of hippocampal dentate granule cells. Precipitating injuries that kill interneurons in the dentate gyrus might result in fewer inhibitory synapses with granule cells. To test this hypothesis, previous studies evaluated numbers or densities of interneurons, γ-amino butyric acid (GABA)ergic boutons, and inhibitory synapses in tissue from human patients with temporal lobe epilepsy and rodent models. However, those studies have limitations. Some of those limitations can be addressed by a large animal model. Sea lions ( Zalophus californianus ) can develop temporal lobe epilepsy naturally. Like humans, epileptic sea lions exhibit bilateral or unilateral hippocampal sclerosis (neuron loss) with granule cell vulnerability, but sea lions permit optimal tissue preservation and sampling, and good control subjects. To label interneuron cell bodies and GABAergic synaptic boutons, sea lion hippocampal tissue from both sexes was processed with imm...

Accurate time estimation is essential for optimizing our perception and actions. Previous neuroimaging and transcranial magnetic stimulation (TMS) studies have suggested that the right inferior parietal lobule (IPL) and supplementary motor area (SMA) are involved in time perception. However, it remains inconclusive whether the activity in these regions is crucial for time perception, partly due to the possible spread of TMS effects across anatomically connected brain regions. Such a remote effect is less likely to happen with transcranial static magnetic stimulation (tSMS), as the static magnetic field is expected to modulate the firing threshold of neurons rather than directly triggering an action potential. In this study, we aimed to determine the causal relevance of local activities in the right IPL and the SMA for temporal processing using tSMS. Forty-eight human volunteers (26 males and 22 females) participated in the study. We measured duration discrimination thresholds, along with orientation discri...

The current treatment for drug-resistant epilepsy is surgical intervention, which relies on accurate identification of the seizure onset zone (SOZ) using intracranial electroencephalography (iEEG) data. iEEG analysis with computational epileptogenic zone identification algorithms (CEZIAs) is a promising step toward better SOZ localization and surgical outcomes. A key step in validation and adoption of CEZIAs is to allow for widespread shared development and validation of code and data. To achieve this, we developed an ecosystem of seizure localization methods that includes a straightforward analysis pipeline, standardized data formatting and storage, and completely documented and open-source code. The TableContainer package provides standardized storage of tabular data and serves as a foundational data structure for the ecosystem. Building on this, the Epoch package enables cropping, resampling, and visualization of iEEG data and provides publicly downloadable datasets for reproducibility. The public iEEG ...

Repeated restraint stress (RRS) in rats impairs cognitive flexibility, particularly when faced with additional mild acute stress (AS). We tested the hypothesis that this impairment is associated with altered dopaminergic activity in the dorsal striatum (DS) driven by corticotropin-releasing-factor receptor type 1 (CRFR1) in the substantia nigra pars compacta (SNpc). Sixty-two male rats received RRS or handling for 14 d, before training on a two-action, two-outcome instrumental conditioning task. Initial learning was assessed using an outcome devaluation test. Cognitive flexibility was assessed by reversing the outcome identities and a second outcome devaluation test, with half the rats in each group receiving AS before reversal training. Dopamine and metabolites were quantified in the DS, and CRFR1 mRNA was quantified in the SNpc. In Experiment 2, SNpc CRFR1 was pharmacologically blocked unilaterally before AS and reversal training in 32 male and 32 female rats. Increased dopaminergic activity in the DS an...

Terry Dean and Vittorio Gallo discuss their paper, “Endogenous Circadian Clock Machinery in Cortical NG2-Glia Regulates Cellular Proliferation,” published in Vol. 9, Issue 5 of eNeuro, with Editor-in-Chief Cristophe Bernard. 

“Rigor” is the vaguest sought-after quality of research. If you attach a license to your work, you can say it’s open. If you guide a collaborator through a protocol, your work is reproducible.

The current treatment for drug-resistant epilepsy is surgical intervention, which relies on accurate identification of the seizure onset zone (SOZ) using intracranial EEG (iEEG) data. iEEG analysis with computational epileptogenic zone identification algorithms (CEZIAs) is a promising step towards better SOZ localization and surgical outcomes. A key step in validation and adoption of CEZIAs is to allow for widespread shared development and validation of code and data. We describe a set of three R packages to achieve this goal. Our ecosystem of seizure localization methods involves a straightforward analysis pipeline, standardized data formatting and storage, and completely documented and open-source code. The TableContainer package allows for easy storage and manipulation of table data, serving as groundwork for the Epoch package, which is specifically geared towards iEEG data. The Epoch package allows for cropping, resampling, and visualization of iEEG data and provides publicly downloadable iEEG data for...

Harmonicity is a property of complex sounds such as vocalizations or music, but it remains unclear how harmonicity is processed in the auditory cortex (ACtx). Subregions of ACtx are thought to process harmonic stimuli differently. Selective responses to sound features in ACtx emerge hierarchically from primary ACtx (A1) L4 and secondary ACtx (A2) layer (L) 2/3, which is believed to be the most responsive to harmonic sounds. Since harmonic stacks can range from two to more than ten components, being more similar to naturalistic vocalizations, harmonic sensitivity might also arise hierarchically across layers and areas. We studied responses to harmonic stacks of two to ten frequencies across A1 L4, A1 L2/3, and A2 L2/3 in adult male and female mice using in vivo two-photon microscopy. We found harmonic-sensitive neurons (HN) responding only to harmonic stacks but not to individual frequencies in all areas at similar proportions. HNs showed highly nonlinear spectral integration of harmonic frequencies that de...

Consumption varies across the stages (metestrus, diestrus, proestrus, estrus) of a rat’s estrous cycle, changing in ways that might be expected to reflect, in part, a direct impact of hormones on taste palatability. Evidence regarding this hypothesis has been mixed, however, and critical within-subject experiments comparing consumption of multiple tastes with distinct valences across all estrous phases have been few. Here, we assayed female rats’ licking of palatable (saccharin, sucrose, NaCl) and aversive (quinine-HCl, citric acid) tastes in brief-access trials, while tracking their estrous cycles through vaginal cytology. We observed sucrose palatability to be high at metestrus, the same phase at which the palatability of the aversive citric acid was low. These patterns were consistent across tastes of similar palatability, despite vast differences between the substances’ receptor mechanisms and central impacts. Together, these results reveal a general (i.e., independent of particular tastant identity) m...