Mitral and tufted cells in the olfactory bulb (OB) act as an input convergence hub and transmit information to higher olfactory areas. Since first characterized, they have been classed as distinct projection neurons based on size and location: laminarly-arranged mitral cells with a diameter larger than 20μm in the mitral layer (ML), and smaller tufted cells spread across both the ML and external plexiform layer (EPL). Recent in vivo work has shown that these neurons encode complementary olfactory information, akin to parallel channels in other sensory systems. Yet, many ex vivo studies still collapse them into a single class, mitral/tufted, when describing their physiological properties and impact on circuit function. Using immunohistochemistry and whole-cell patch clamp electrophysiology in fixed or acute slices from adult mice, we attempted to align in vivo and ex vivo data and test a soma size-based classifier of OB projection neurons using passive and intrinsic firing properties. We found that there is no clear separation between cell types based on passive or active properties. Rather, there is a heterogeneous continuum with three loosely clustered subgroups: EPL tufted cells, and putative tufted or putative mitral cells in the ML. These findings illustrate the large functional heterogeneity present within the OB projection neurons and complement existing literature highlighting how heterogeneity in sensory systems is preponderant and possibly used in the OB to decode complex olfactory information. Significance statement Mitral and tufted cells in the olfactory bulb have traditionally been either grouped due to their shared role in early odour processing, or separated into distinct groups based on in vivo physiology and circuit connectivity. However, our ex vivo study in post-weaning mice reveals a more complex picture. Rather than being clearly distinct or identical, mitral and tufted cells form a diverse continuum of morphological and functional properties. This variability may enable efficient processing of the wide range of odours animals encounter. These findings highlight the importance of considering nuanced differences when classifying neurons in the olfactory bulb and more broadly in the brain.
Abstract Mitral and tufted cells in the olfactory bulb (OB) act as an input convergence hub and transmit information to higher olfactory areas. Since first characterized, they have been classed as distinct projection neurons based on size and location: laminarly-arranged mitral cells with a diameter larger than 20µm in the mitral layer (ML), and smaller tufted cells spread across both the ML and external plexiform layer (EPL). Recent in vivo work has shown that these neurons encode complementary olfactory information, akin to parallel channels in other sensory systems. Yet, many ex vivo studies still collapse them into a single class, mitral/tufted, when describing their physiological properties and impact on circuit function. Using immunohistochemistry and whole-cell patch clamp electrophysiology in fixed or acute slices from adult mice, we attempted to align in viv o and ex vivo data and test a soma size-based classifier of OB projection neurons using passive and intrinsic firing properties. We found that there is no clear separation between cell types based on passive or active properties. Rather, there is a heterogeneous continuum with three loosely clustered subgroups: EPL tufted cells, and putative tufted or putative mitral cells in the ML. These findings illustrate the large functional heterogeneity present within the OB projection neurons and complement existing literature highlighting how heterogeneity in sensory systems is preponderant and possibly used in the OB to decode complex olfactory information.
Abstract Dopaminergic (DA) neurons play pivotal roles in diverse brain functions, spanning movement, reward processing, and sensory perception. DA neurons are most abundant in the midbrain (Substantia Nigra pars compacta, SNC, and Ventral Tegmental Area, VTA) and the olfactory bulb (OB) in the forebrain. Interestingly, a subtype of OB DA neurons is capable of regenerating throughout life, while a second class is exclusively born during embryonic development. Emerging evidence in SNC and VTA also indicates substantial heterogeneity in terms of morphology, connectivity, and function. To further investigate this heterogeneity and directly compare form and function of midbrain and forebrain DA neurons, we performed immunohistochemistry and whole-cell patch-clamp recordings in ex vivo brain slices from juvenile DAT-tdTomato mice. After confirming the penetrance and specificity of the dopamine transporter (DAT) Cre line, we compared soma shape, passive membrane properties, voltage sags and action potential firing across midbrain and forebrain DA subtypes. We found that each DA subgroup within midbrain and forebrain was highly heterogeneous, and that DA neurons across the two brain areas are also substantially different. These findings complement previous work in rats as well as gene expression and in vivo datasets, further questioning the existence of a single “dopaminergic” neuronal phenotype.
Abstract Dopaminergic (DA) neurons play pivotal roles in diverse brain functions, spanning movement, reward processing and sensory perception. DA neurons are most abundant in the midbrain (Substantia Nigra pars compacta [SNC] and Ventral Tegmental Area [VTA]) and the olfactory bulb (OB) in the forebrain. Interestingly, a subtype of OB DA neurons is capable of regenerating throughout life, while a second class is exclusively born during embryonic development. Compelling evidence in SNC and VTA also indicates substantial heterogeneity in terms of morphology, connectivity and function. To further investigate this heterogeneity and directly compare form and function of midbrain and forebrain bulbar DA neurons, we performed immunohistochemistry and whole‐cell patch‐clamp recordings in ex vivo brain slices from juvenile DAT‐tdTomato mice. After confirming the penetrance and specificity of the dopamine transporter (DAT) Cre line, we compared soma shape, passive membrane properties, voltage sags and action potential (AP) firing across midbrain and forebrain bulbar DA subtypes. We found that each DA subgroup within midbrain and OB was highly heterogeneous, and that DA neurons across the two brain areas are also substantially different. These findings complement previous work in rats as well as gene expression and in vivo datasets, further questioning the existence of a single “dopaminergic” neuronal phenotype.
Dopaminergic (DA) neurons play pivotal roles in diverse brain functions, spanning movement, reward processing, and sensory perception. DA neurons are most abundant in the midbrain (Substantia Nigra pars compacta, SNC, and Ventral Tegmental Area, VTA) and the olfactory bulb (OB) in the forebrain. Interestingly, a subtype of OB DA neurons is capable of regenerating throughout life, while a second class is exclusively born during embryonic development. Emerging evidence in SNC and VTA also indicates substantial heterogeneity in terms of morphology, connectivity, and function. To further investigate this heterogeneity and directly compare form and function of midbrain and forebrain DA neurons, we performed immunohistochemistry and whole-cell patch-clamp recordings in ex vivo brain slices from juvenile DAT-tdTomato mice. After confirming the penetrance and specificity of the dopamine transporter (DAT) Cre line, we compared soma shape, passive membrane properties, voltage sags and action potential firing across midbrain and forebrain DA subtypes. We found that each DA subgroup within midbrain and forebrain was highly heterogeneous, and that DA neurons across the two brain areas are also substantially different. These findings complement previous work in rats as well as gene expression and in vivo datasets, further questioning the existence of a single “dopaminergic” neuronal phenotype.
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