Cortex-wide response mode of VIP-expressing inhibitory neurons by reward and punishment

Neocortex is classically divided into distinct areas, each specializing in different function, but all could benefit from reinforcement feedback to inform and update local processing. Yet it remains elusive how global signals like reward and punishment are represented in local cortical computations. Previously, we identified a cortical neuron type, vasoactive intestinal polypeptide (VIP)-expressing interneurons, in auditory cortex that is recruited by behavioral reinforcers and mediates disinhibitory control by inhibiting other inhibitory neurons. As the same disinhibitory cortical circuit is present virtually throughout cortex, we wondered whether VIP neurons are likewise recruited by reinforcers throughout cortex. We monitored VIP neural activity in dozens of cortical regions using three-dimensional random access two-photon microscopy and fiber photometry while mice learned an auditory discrimination task. We found that reward and punishment during initial learning produce rapid, cortex-wide activation of most VIP interneurons. This global recruitment mode showed variations in temporal dynamics in individual neurons and across areas. Neither the weak sensory tuning of VIP interneurons in visual cortex nor their arousal state modulation was fully predictive of reinforcer responses. We suggest that the global response mode of cortical VIP interneurons supports a cell-type-specific circuit mechanism by which organism-level information about reinforcers regulates local circuit processing and plasticity

Cortex-wide response mode of VIP-expressing inhibitory neurons by reward and punishment

Neocortex is classically divided into distinct areas, each specializing in different function, but all could benefit from reinforcement feedback to inform and update local processing. Yet it remains elusive how global signals like reward and punishment are represented in local cortical computations. Previously, we identified a cortical neuron type, vasoactive intestinal polypeptide (VIP)-expressing interneurons, in auditory cortex that is recruited by behavioral reinforcers and mediates disinhibitory control by inhibiting other inhibitory neurons. As the same disinhibitory cortical circuit is present virtually throughout cortex, we wondered whether VIP neurons are likewise recruited by reinforcers throughout cortex. We monitored VIP neural activity in dozens of cortical regions using three-dimensional random access two-photon microscopy and fiber photometry while mice learned an auditory discrimination task. We found that reward and punishment during initial learning produce rapid, cortex-wide activation of most VIP interneurons. This global recruitment mode showed variations in temporal dynamics in individual neurons and across areas. Neither the weak sensory tuning of VIP interneurons in visual cortex nor their arousal state modulation was fully predictive of reinforcer responses. We suggest that the global response mode of cortical VIP interneurons supports a cell-type-specific circuit mechanism by which organism-level information about reinforcers regulates local circuit processing and plasticity

LED Arrays as Cost Effective and Efficient Light Sources for Widefield Microscopy

New developments in fluorophores as well as in detection methods have fueled the rapid growth of optical imaging in the life sciences. Commercial widefield microscopes generally use arc lamps, excitation/emission filters and shutters for fluorescence imaging. These components can be expensive, difficult to maintain and preclude stable illumination. Here, we describe methods to construct inexpensive and easy-to-use light sources for optical microscopy using light-emitting diodes (LEDs). We also provide examples of its applicability to biological fluorescence imaging

Mapping odorant receptors to their glomeruli

Wang et al. used transcriptomic profiles of olfactory sensory neurons to determine the identity of their odorant receptors and map the location of their corresponding glomeruli on the olfactory bulb surface. The method enables high-throughput molecular mapping of the glomerular layout and opens up new venues to understand olfactory processing

A non-canonical feedforward pathway for computing odor identity

AbstractSensory systems rely on statistical regularities in the experienced inputs to either group disparate stimuli, or parse them into separate categories1,2. While considerable progress has been made in understanding invariant object recognition in the visual system3–5, how this is implemented by olfactory neural circuits remains an open question6–10. The current leading model states that odor identity is primarily computed in the piriform cortex, drawing from mitral cell (MC) input6–9,11. Surprisingly, the role of tufted cells (TC)12–16, the other principal cell-type of the olfactory bulb (OB) in decoding odor identity, and their dependence on cortical feedback, has been overlooked. Tufted cells preferentially project to the anterior olfactory nucleus (AON) and olfactory striatum, while mitral cells strongly innervate the piriform cortex (PC). Here we show that classifiers based on the population activity of tufted cells successfully decode both odor identity and intensity across a large concentration range. In these computations, tufted cells substantially outperform mitral cells, and are largely unaffected by silencing of cortical feedback. Further, cortical feedback from AON controls preferentially the gain of tufted cell odor representations, while PC feedback specifically restructures mitral cell responses, matching biases in feedforward connectivity. Leveraging cell-type specific analyses, we identify a non-canonical feedforward pathway for odor recognition and discrimination mediated by the tufted cells, and propose that OB target areas, other than the piriform cortex, such as AON and olfactory striatum, are well-positioned to compute odor identity.</jats:p

Long-range functional loops in the mouse olfactory system and their roles in computing odor identity

Elucidating the neural circuits supporting odor identification remains an open challenge. Here, we analyze the contribution of the two output cell types of the mouse olfactory bulb (mitral and tufted cells) to decode odor identity and concentration and its dependence on top-down feedback from their respective major cortical targets: piriform cortex versus anterior olfactory nucleus. We find that tufted cells substantially outperform mitral cells in decoding both odor identity and intensity. Cortical feedback selectively regulates the activity of its dominant bulb projection cell type and implements different computations. Piriform feedback specifically restructures mitral responses, whereas feedback from the anterior olfactory nucleus preferentially controls the gain of tufted representations without altering their odor tuning. Our results identify distinct functional loops involving the mitral and tufted cells and their cortical targets. We suggest that in addition to the canonical mitral-to-piriform pathway, tufted cells and their target regions are ideally positioned to compute odor identity