Developmental, cellular, and subcellular variations in the direction of neuronal Cl– currents elicited by GABAA receptor activation have been frequently reported. We found a corresponding variance in the GABAA receptor reversal potential (EGABA) for synapses originating from individual interneurons onto a single pyramidal cell. These findings suggest a similar heterogeneity in the cytoplasmic intracellular concentration of chloride ([Cl–]i) in individual dendrites. We determined [Cl–]i in the murine hippocampus and cerebral cortex of both sexes by (1) two-photon imaging of the Cl–-sensitive, ratiometric fluorescent protein SuperClomeleon; (2) Fluorescence Lifetime IMaging (FLIM) of the Cl–-sensitive fluorophore MEQ (6-methoxy- N -ethylquinolinium); and (3) electrophysiological measurements of EGABA by pressure application of GABA and RuBi-GABA uncaging. Fluorometric and electrophysiological estimates of local [Cl–]i were highly correlated. [Cl–]i microdomains persisted after pharmacological inhibition of c...

Quantitative estimations of spatiotemporal complexity of cortical activity patterns are used in the clinic as a measure of consciousness levels, but the cortical mechanisms involved are not fully understood. We used a version of the perturbational complexity index (PCI) adapted to multisite recordings from the ferret (either sex) cerebral cortex in vitro (sPCI) to investigate the role of GABAergic inhibition in cortical complexity. We studied two dynamical states: slow-wave activity (synchronous state) and desynchronized activity, that express low and high causal complexity respectively. Progressive blockade of GABAergic inhibition during both regimes revealed its impact on the emergent cortical activity and on sPCI. Gradual GABAA receptor blockade resulted in higher synchronization, being able to drive the network from a desynchronized to a synchronous state, with a progressive decrease of complexity (sPCI). Blocking GABAB receptors also resulted in a reduced sPCI, in particular when in a synchronous, slo...

Everyday decision-making commonly involves assigning values to complex objects with multiple value-relevant attributes. Drawing on object recognition theories, we hypothesized two routes to multiattribute evaluation: assessing the value of the whole object based on holistic attribute configuration or summing individual attribute values. In two samples of healthy human male and female participants undergoing eye tracking and functional magnetic resonance imaging (fMRI) while evaluating novel pseudo objects, we found evidence for both forms of evaluation. Fixations to and transitions between attributes differed systematically when the value of pseudo objects was associated with individual attributes or attribute configurations. Ventromedial prefrontal cortex (vmPFC) and perirhinal cortex were engaged when configural processing was required. These results converge with our recent findings that individuals with vmPFC lesions were impaired in decisions requiring configural evaluation but not when evaluating the...

Understanding speech in background noise is a difficult task. The tracking of speech rhythms such as the rate of syllables and words by cortical activity has emerged as a key neural mechanism for speech-in-noise comprehension. In particular, recent investigations have used transcranial alternating current stimulation (tACS) with the envelope of a speech signal to influence the cortical speech tracking, demonstrating that this type of stimulation modulates comprehension and therefore providing evidence of a functional role of the cortical tracking in speech processing. Cortical activity has been found to track the rhythms of a background speaker as well, but the functional significance of this neural response remains unclear. Here we use a speech-comprehension task with a target speaker in the presence of a distractor voice to show that tACS with the speech envelope of the target voice as well as tACS with the envelope of the distractor speaker both modulate the comprehension of the target speech. Because t...

Seeing a speaker's face benefits speech comprehension, especially in challenging listening conditions. This perceptual benefit is thought to stem from the neural integration of visual and auditory speech at multiple stages of processing, whereby movement of a speaker's face provides temporal cues to auditory cortex, and articulatory information from the speaker's mouth can aid recognizing specific linguistic units (e.g., phonemes, syllables). However, it remains unclear how the integration of these cues varies as a function of listening conditions. Here, we sought to provide insight on these questions by examining EEG responses in humans (males and females) to natural audiovisual (AV), audio, and visual speech in quiet and in noise. We represented our speech stimuli in terms of their spectrograms and their phonetic features and then quantified the strength of the encoding of those features in the EEG using canonical correlation analysis (CCA). The encoding of both spectrotemporal and phonetic features was ...

Mutations on γ-secretase subunits are associated with neurologic diseases. Whereas the role of γ-secretase in neurogenesis has been intensively studied, little is known about its role in astrogliogenesis. Recent evidence has demonstrated that astrocytes can be generated from oligodendrocyte precursor cells (OPCs). However, it is not well understood what mechanism may control OPCs to differentiate into astrocytes. To address the above questions, we generated two independent lines of oligodendrocyte lineage-specific presenilin enhancer 2 ( Pen-2 ) conditional KO mice. Both male and female mice were used. Here we demonstrate that conditional inactivation of Pen-2 mediated by Olig1-Cre or NG2-CreERT2 causes enhanced generation of astrocytes. Lineage-tracing experiments indicate that abnormally generated astrocytes are derived from Cre-expressing OPCs in the CNS in Pen-2 conditional KO mice. Mechanistic analysis reveals that deletion of Pen-2 inhibits the Notch signaling to upregulate signal transducer and acti...

Double cones are the most common photoreceptor cell type in most avian retinas, but their precise functions remain a mystery. Among their suggested functions are luminance detection, polarized light detection, and light-dependent, radical pair-based magnetoreception. To better understand the function of double cones, it will be crucial to know how they are connected to the neural network in the avian retina. Here we use serial sectioning, multibeam scanning electron microscopy to investigate double-cone anatomy and connectivity with a particular focus on their contacts to other photoreceptor and bipolar cells in the chicken retina. We found that double cones are highly connected to neighboring double cones and with other photoreceptor cells through telodendria-to-terminal and telodendria-to-telodendria contacts. We also identified 15 bipolar cell types based on their axonal stratifications, photoreceptor contact pattern, soma position, and dendritic and axonal field mosaics. Thirteen of these 15 bipolar ce...

Control of protein intake is essential for numerous biological processes as several amino acids cannot be synthesized de novo, however, its neurobiological substrates are still poorly understood. In the present study, we combined in vivo fiber photometry with nutrient-conditioned flavor in a rat model of protein appetite to record neuronal activity in the VTA, a central brain region for the control of food-related processes. In adult male rats, protein restriction increased preference for casein (protein) over maltodextrin (carbohydrate). Moreover, protein consumption was associated with a greater VTA response, relative to carbohydrate. After initial nutrient preference, a switch from a normal balanced diet to protein restriction induced rapid development of protein preference but required extensive exposure to macronutrient solutions to induce elevated VTA responses to casein. Furthermore, prior protein restriction induced long-lasting food preference and VTA responses. This study reveals that VTA circuit...

Negah Rahmati, Kieran P. Normoyle, Joseph Glykys, Volodymyr I. Dzhala, Kyle P. Lillis, et al. (see pages [4957–4975][1]) GABAergic receptors form the cornerstone of inhibitory synaptic signaling in the brain. Classically, ionotropic GABAA receptors pass inward chloride-dominated currents,

There is a major debate regarding the function of the thalamus: does the thalamus solely gate the transmission of information or is it actively involved in processing information? [Sherman and Guillery (2006)][1] argued that thalamic nuclei function as bidirectional relays for the flow of