Decision-making is traditionally described as a cognitive process of deliberation followed by commitment to an action choice, preceding the planning and execution of the chosen action. However, this is challenged by recent data suggesting that during situated decisions, multiple options are specified simultaneously and compete in pre-motor cortical areas for selection and execution. Previous studies focused on the competition during planning, and leave unaddressed the dynamics of decisions during movement. Does deliberation extend into the execution phase? Are non-selected options still considered? Here we studied a decision-making task in which human participants were instructed to select a reaching path trajectory from an origin to a rectangular target, where reward was distributed non-uniformly at the target. Critically, we applied mechanical perturbations to the arm during movement to study under which conditions such perturbations produce changes of mind. Our results show that participants initially s...

Excitatory amino acid transporters (EAATs) remove glutamate from the synaptic cleft. In the retina, EAAT1 and EAAT2 are considered the major glutamate transporters. However, it has not yet been possible to determine how EAAT5 shapes the retinal light responses because of the lack of a selective EAAT5 blocker or EAAT5 knock-out animal model. In this study, EAAT5 was found to be expressed in a punctate manner close to release sites of glutamatergic synapses in the mouse retina. Light responses from retinae of wild-type and of a newly generated model with a targeted deletion of EAAT5 (EAAT5-/-) were recorded in vitro using multi-electrode arrays. Flicker resolution was considerably lower in EAAT5-/- retinae than in wild-type retinae. The close proximity to the glutamate release site makes EAAT5 an ideal tool to improve temporal information processing in the retina by controlling information transfer at glutamatergic synapses. Significance statement Neurons communicate with other neurons at synaptic connect...

A series of studies in which monkeys chose between two juices offered in variable amounts identified in the orbitofrontal cortex (OFC) different groups of neurons encoding the value of individual options ( offer value ), the binary choice outcome ( chosen juice ) and the chosen value . These variables capture both the input and the output of the choice process, suggesting that the cell groups identified in OFC constitute the building blocks of a decision circuit. Several lines of evidence support this hypothesis. However, in previous experiments offers were presented simultaneously, raising the question of whether current notions generalize to when goods are presented or are examined in sequence. Recently, Ballesta and Padoa-Schioppa (2019) examined OFC activity under sequential offers. An analysis of neuronal responses across time windows revealed that a small number of cell groups encoded specific sequences of variables. These sequences appeared analogous to the variables identified under simultaneous of...

Temporal coherence of sound fluctuations across spectral channels is thought to aid auditory grouping and scene segregation. Although prior studies on the neural bases of temporal-coherence processing focused mostly on cortical contributions, neurophysiological evidence suggests that temporal-coherence-based scene analysis may start as early as the cochlear nucleus (i.e., the first auditory region supporting cross-channel processing over a wide frequency range). Accordingly, we hypothesized that aspects of temporal-coherence processing that could be realized in early auditory areas may shape speech understanding in noise. We then explored whether physiologically plausible computational models could account for results from a behavioral experiment that measured consonant categorization in different masking conditions. We tested whether within-channel masking of target-speech modulations predicted consonant confusions across the different conditions and whether predictions were improved by adding across-chan...

Appropriate responding to threat and reward is essential to survival. The nucleus accumbens core (NAcc) is known to support and organize reward behavior. The NAcc is also necessary to fully discriminate threat and safety cues. To directly reveal NAcc threat firing, we recorded single-unit activity from 7 female rats undergoing Pavlovian fear discrimination. Rats fully discriminated danger, uncertainty, and safety cues, and most NAcc neurons showed greatest firing change to danger and uncertainty. Heterogeneity in cue and reward firing led us to identify distinct functional populations. One NAcc population signaled threat, specifically decreasing firing to danger and uncertainty cues. A separate population signaled bidirectional valence, decreasing firing to the danger cue (negative valence), but increasing firing to reward (positive valence). The results reveal the NAcc to be a source of threat information and a more general valence hub. SIGNIFICANCE STATEMENT The nucleus accumbens core (NAcc) is synony...

Sensorimotor circuits of the lumbosacral spinal cord are required for lower urinary tract (LUT) regulation as well as being engaged in pelvic pain states. To date, no molecular markers have been identified to enable specific visualization of LUT afferents, which are embedded within spinal cord segments that also subserve somatic functions. Moreover, previous studies have not fully investigated the patterning within or across spinal segments, compared afferent innervation of the bladder and urethra, or explored possible structural sex differences in these pathways. We have addressed these questions in adult Sprague-Dawley rats, using intramural microinjection of the tract tracer, cholera toxin B subunit. Afferent distribution was analysed within individual sections and 3D reconstructions from sections across four spinal cord segments (L5-S2), and in cleared intact spinal cord viewed with light sheet microscopy. Simultaneous mapping of preganglionic neurons showed their location throughout S1 but restricted ...

The local circuitry within olfactory bulb glomeruli filters, transforms, and facilitates information transfer from olfactory sensory neurons to bulb output neurons. Two key elements of this circuit are glutamatergic tufted cells (TCs) and GABAergic periglomerular (PG) cells, both of which actively shape mitral cell activity and bulb output. A subtype of TCs, the external tufted cells (eTCs), can synaptically excite PG cells, but there are unresolved questions about other aspects of the glomerular connections, including the extent of connectivity between eTCs and the precise nature of reciprocal interactions between TCs and PG cells. We combined patch-clamp recordings in OB slices and optophysiological tools to investigate local functional connections within glomeruli of mice and rats. When TCs that express cholecystokinin (CCK) were optically suppressed, excitatory post-synaptic currents (EPSCs) in “uniglomerular” PG cells that extend dendrites to one glomerulus were decreased, consistent with TC activatio...

Neurotoxic HIV-1 viral proteins contribute to the development of HIV-associated neurocognitive disorders (HAND), the prevalence of which remains high (30 to 50%) with no effective treatment is available. Estrogen is a known neuroprotective agent; however, the diverse mechanisms of estrogen action on the different types of estrogen receptors is not completely understood. In this study, we determined the extent to which and mechanisms by which 17α-estradiol (17αE2), a natural less-feminizing estrogen, offers neuroprotection against HIV-1 gp120-induced neuronal injury. Endolysosomes are important for neuronal function and endolysosomal dysfunction contributes to HAND and other neurodegenerative disorders. In hippocampal neurons, estrogen receptor alpha (ERα) is localized to endolysosomes and 17αE2 acidifies endolysosomes. ERα knockdown or over-expressing an ERα mutant that is deficient in endolysosome localization prevents 17αE2-induced endolysosome acidification. Furthermore, 17αE2-induced increases in dendr...

A fundamental regulator of neuronal network development and plasticity is the extracellular matrix (ECM) of the brain. The ECM provides a scaffold stabilizing synaptic circuits, while the proteolytic cleavage of its components and cell surface proteins are thought to have permissive roles in the regulation of plasticity. The enzymatic proteolysis is thought to be crucial for homeostasis between stability and reorganizational plasticity and facilitated largely by a family of proteinases named matrix metalloproteinases (MMPs). Here, we investigated whether MMP2 and MMP9 play a role in mediating adult primary visual cortex (V1) plasticity as well as stroke-induced impairments of visual cortex plasticity in mice. In healthy adult mice, selective inhibition of MMP2/9 for 7 d suppressed ocular dominance plasticity (ODP). In contrast, brief inhibition of MMP2/9 after a cortical stroke rescued compromised plasticity. Our data indicate that the proteolytic activity of MMP2 and MMP9 is critical and required to be wi...

Space specific neurons in the owl's midbrain form a neural map of auditory space, which supports sound orienting behavior. Previous work proposed that a population vector (PV) readout of this map, implementing statistical inference, predicts the owl's sound localization behavior. This model also predicts the frontal localization bias normally observed and how sound localizing behavior changes when the signal to noise ratio varies, based on the spread of activity across the map. However, the actual distribution of population activity and whether this pattern is consistent with premises of the PV readout model on a trial-by-trial bases remains unknown. To answer these questions, we investigated whether the population response profile across the midbrain map in the barn owl's optic tectum matches these predictions using in vivo multi-electrode array recordings. We found that response profiles of recorded sub-populations are sufficient for estimating the stimulus ITD using responses from single trials. Further...