Parvalbumin-positive (Pvalb+) and somatostatin-positive (Sst+) cells are the two largest subgroups of inhibitory interneurons. Studies in visual cortex indicate that synaptic connections between Pvalb+ cells are common while connections between Sst+ interneurons have not been observed. The inhibitory connectivity and kinetics of these two interneuron subpopulations, however, have not been characterized in medial entorhinal cortex (mEC). Using fluorescence-guided paired recordings in mouse brain slices from interneurons and excitatory cells in layer 2/3 mEC, we found that, unlike neocortical measures, Sst+ cells inhibit each other, albeit with a lower probability than Pvalb+ cells (18% vs 36% for unidirectional connections). Gap junction connections were also more frequent between Pvalb+ cells than between Sst+ cells. Pvalb+ cells inhibited each other with larger conductances, smaller decay time constants, and shorter delays. Similarly, synaptic connections between Pvalb+ and excitatory cells were more like...

G-protein-coupled receptors (GPCRs) coupled to Gi signaling, in particular downstream of monoaminergic neurotransmission, are posited to play a key role during developmental epochs (postnatal and juvenile) in shaping the emergence of adult anxiodepressive behaviors and sensorimotor gating. To address the role of Gi signaling in these developmental windows, we used a CaMKIIα-tTA::TRE hM4Di bigenic mouse line to express the hM4Di-DREADD (designer receptor exclusively activated by designer drugs) in forebrain excitatory neurons and enhanced Gi signaling via chronic administration of the DREADD agonist, clozapine- N -oxide (CNO) in the postnatal window (postnatal days 2–14) or the juvenile window (postnatal days 28–40). We confirmed that the expression of the HA-tagged hM4Di-DREADD was restricted to CaMKIIα-positive neurons in the forebrain, and that the administration of CNO in postnatal or juvenile windows evoked inhibition in forebrain circuits of the hippocampus and cortex, as indicated by a decline in exp...

Spontaneous α oscillations (∼10 Hz) have been associated with various cognitive functions, including perception. Their phase and amplitude independently predict cortical excitability and subsequent perceptual performance. However, the causal role of α phase-amplitude tradeoffs on visual perception remains ill-defined. We aimed to fill this gap and tested two clear predictions from the pulsed inhibition theory according to which α oscillations are associated with periodic functional inhibition. (1) High-α amplitude induces cortical inhibition at specific phases, associated with low perceptual performance, while at opposite phases, inhibition decreases (potentially increasing excitation) and perceptual performance increases. (2) Low-α amplitude is less susceptible to these phasic (periodic) pulses of inhibition, leading to overall higher perceptual performance. Here, cortical excitability was assessed in humans using phosphene (illusory) perception induced by single pulses of transcranial magnetic stimulatio...

Collaboration in neuroscience is impeded by the difficulty of sharing primary data, results, and software across labs. Here, we introduce Neuroscience Data Interface (NDI), a platform-independent standard that allows an analyst to use and create software that functions independently from the format of the raw data or the manner in which the data are organized into files. The interface is rooted in a simple vocabulary that describes common apparatus and storage devices used in neuroscience experiments. Results of analyses, and analyses of analyses, are stored as documents in a scalable, queryable database that stores the relationships and history among the experiment elements and documents. The interface allows the development of an application ecosystem where applications can focus on calculation rather than data format or organization. This tool can be used by individual labs to exchange and analyze data, and it can serve to curate neuroscience data for searchable archives.

To understand how vowels are encoded by auditory nerve (AN) fibers, a number of representation schemes have been suggested that extract the vowel’s formant frequencies from AN-fiber spiking patterns. The current study aims to apply and compare these schemes for AN-fiber responses to naturally-spoken vowels in a speech-shaped background noise. Responses to three vowels were evaluated; based on behavioral experiments in the same species, two of these were perceptually difficult to discriminate from each other (/e/ vs /i/), and one was perceptually easy to discriminate from the other two (/a:/). Single-unit AN fibers were recorded from ketamine/xylazine-anesthetized Mongolian gerbils of either sex ( n  = 8). First, single-unit discrimination between the three vowels was studied. Compared with the perceptually easy discriminations, the average spike timing-based discrimination values were significantly lower for the perceptually difficult vowel discrimination. This was not true for an average rate-based discri...

Operant chambers are widely used in animal research to study cognition, motivation, and learning processes. Paired with the rapidly developing technologies for brain imaging and manipulations of brain activity, operant conditioning chambers are a powerful tool for neuroscience research. The behavioral testing and imaging setups that are commercially available are often quite costly. Here, we present a custom-built operant chamber that can be constructed in a few days by an unexperienced user with relatively inexpensive, widely available materials. The advantages of our operant setup compared with other open-source and closed-source solutions are its relatively low cost, its support of complex behavioral tasks, its user-friendly setup, and its validated functionality with video imaging of behavior and calcium imaging using the UCLA Miniscope. Using this setup, we replicate our previously published findings showing that mice exposed to social defeat stress in adolescence have inhibitory control impairments i...

Bulimia nervosa (BN) and binge eating disorder (BED) are characterized by episodes of eating large amounts of food while experiencing a loss of control. Recent studies suggest that the underlying causes of BN/BED consist of a complex system of environmental cues, atypical processing of food stimuli, altered behavioral responding, and structural/functional brain differences compared with healthy controls (HC). In this narrative review, we provide an integrative account of the brain networks associated with the three cognitive constructs most integral to BN and BED, namely increased reward sensitivity, decreased cognitive control, and altered negative affect and stress responding. We show altered activity in BED/BN within several brain networks, specifically in the striatum, insula, prefrontal cortex (PFC) and orbitofrontal cortex (OFC), and cingulate gyrus. Numerous key nodes in these networks also differ in volume and connectivity compared with HC. We provide suggestions for how this integration may guide ...

Postnatal CNS development is fine-tuned to drive the functional needs of succeeding life stages; accordingly, the emergence of sensory and motor functions, behavioral patterns and cognitive abilities relies on a complex interplay of signaling pathways. Strictly regulated Ca2+ signaling mediated by L-type channels (LTCCs) is crucial in neural circuit development and aberrant increases in neuronal LTCC activity are linked to neurodevelopmental and psychiatric disorders. In the amygdala, a brain region that integrates signals associated with aversive and rewarding stimuli, LTCCs contribute to NMDA-independent long-term potentiation (LTP) and are required for the consolidation and extinction of fear memory. In vitro studies have elucidated distinct electrophysiological and synaptic properties characterizing the transition from immature to functionally mature basolateral subdivision of the amygdala (BLA) principal neurons. Further, acute increase of LTCC activity selectively regulates excitability and spontaneo...

Regeneration can occur in peripheral neurons after injury, but the mechanisms involved are not fully delineated. Macrophages in dorsal root ganglia (DRGs) are involved in the enhanced regeneration that occurs after a conditioning lesion (CL), but how macrophages stimulate this response is not known. Oncomodulin (Ocm) has been proposed as a proregenerative molecule secreted by macrophages and neutrophils, is expressed in the DRG after axotomy, and stimulates neurite outgrowth by DRG neurons in culture. Wild-type (WT) and Ocm knock-out (KO) mice were used to investigate whether Ocm plays a role in the CL response in DRG neurons after sciatic nerve transection. Neurite outgrowth was measured after 24 and 48 h in explant culture 7 d after a CL. Sciatic nerve regeneration was also measured in vivo 7 d after a CL and 2 d after a subsequent sciatic nerve crush. The magnitude of the increased neurite outgrowth following a CL was significantly smaller in explants from Ocm KO mice than in explants from WT mice. In v...

In his editorial entitled “On Fallacies in Neuroscience,” Bernard (2020) takes his fellow neuroscientists to task for failures in logic that lead to the promulgation of fallacies and their entrenchment in the scientific literature. Drawing on his background in mathematics and philosophy, he highlights two common errors in logic that permeate our field. The first error he discusses leads to a fallacy known as “reverse inference.” The example he cites is subtle, but all the more telling because it “feels” correct before we are shown the problem. Imagine that my brain is in a scanner when I experience a bout of fear. The scan shows that a particular brain region (Bernard calls it Area Z) lights up brightly with the onset of my fear. One would be correct in proposing that Area Z is likely involved in my brain's processing of fear. The fallacious conclusion, however, would be to assert that if Area Z is lit, I must be experiencing fear. That is the “reverse” of the experimental design, which was to induce fear...