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 In many brain regions involved in learning NMDA receptors (NMDARs) act as coincidence detectors of pre- and postsynaptic activity, mediating Hebbian plasticity. Intriguingly, the parallel fiber (PF) to Purkinje cell (PC) input in the cerebellar cortex, which is critical for procedural learning, shows virtually no postsynaptic NMDARs. Why is this? Here, we address this question by generating and testing independent transgenic lines that overexpress NMDAR containing the type 2B subunit (NR2B) specifically in PCs. PCs of the mice that show larger NMDA-mediated currents than controls at their PF input suffer from a blockage of long-term potentiation (LTP) at their PF-PC synapses, while long-term depression (LTD) and baseline transmission are unaffected. Moreover, introducing NMDA-mediated currents affects cerebellar learning in that phase-reversal of the vestibulo-ocular reflex (VOR) is impaired. Our results suggest that under physiological circumstances PC spines lack NMDARs postsynaptically at their PF input so as to allow LTP to contribute to motor learning.
Abstract Most neurogenesis in the mammalian brain is completed embryonically, but in certain areas the production of neurons continues throughout postnatal life. The functional properties of mature postnatally-generated neurons often match those of their embryonically-produced counterparts. However, we show here that in the olfactory bulb (OB), embryonic and postnatal neurogenesis produce functionally distinct subpopulations of dopaminergic (DA) neurons. We define two subclasses of OB DA neuron by the presence or absence of a key subcellular specialisation: the axon initial segment (AIS). Large AIS-positive axon-bearing DA neurons are exclusively produced during early embryonic stages, leaving small anaxonic AIS-negative cells as the only DA subtype generated via adult neurogenesis. These populations are functionally distinct: large DA cells are more excitable, yet display weaker and – for certain long-latency or inhibitory events – more broadly-tuned responses to odorant stimuli. Embryonic and postnatal neurogenesis can therefore generate distinct neuronal subclasses, placing important constraints on the functional roles of adult-born neurons in sensory processing.
In addition to its well established role in motor coordination, the cerebellum has been hypothesized to be involved in the control of cognitive and emotional functions. Although a cerebellar contribution to nonmotor functions has been supported by recent studies in human and monkey, it remains to be clarified with an in-depth, systematic approach in mouse mutants. Here we subjected four different cerebellar cell-specific mouse lines whereby the excitatory or inhibitory input to Purkinje cells (PCs) and/or PC postsynaptic plasticity were compromised, to a wide battery of standard cognitive and emotional tests. The four lines, which have all been shown to suffer from impaired motor learning without being ataxic, were tested for social behavior using a sociability task, for spatial navigation using the Morris watermaze, for fear responses using contextual and cued conditioning, and general anxiety using the open-field task. None of the four cerebellum-specific genetic perturbations showed significantly impaired cognitive or emotional behavior. In fact, even without correction for multiple comparisons, only 5 of 154 statistical comparisons showed a marginally significant deficit. Therefore, our data indicate that none of the perturbations of cerebellar functioning studied here affected the cognitive or emotional tests we used. This suggests that there may be a differential impact of the murine and human cerebellum on nonmotor functions. We hypothesize that these differences could be a consequence of the remarkable enlargement of the cerebellar hemispheres during the latest phase of vertebrate phylogeny, which occurred in parallel with the evolution of the cerebral cortex.
Activity-dependent neuronal plasticity is crucial for animals to adapt to dynamic sensory environments. Traditionally, it has been investigated using deprivation approaches in animal models primarily in sensory cortices. Nevertheless, emerging evidence emphasizes its significance in sensory organs and in sub-cortical regions where cranial nerves relay information to the brain. Additionally, critical questions started to arise. Do different sensory modalities share common cellular mechanisms for deprivation-induced plasticity at these central entry-points? Does the deprivation duration correlate with specific plasticity mechanisms? This study systematically reviews and meta-analyses research papers that investigated visual, auditory, or olfactory deprivation in rodents of both sexes. It examines the consequences of sensory deprivation in homologous regions at the first central synapse following cranial nerve transmission (vision-lateral geniculate nucleus and superior colliculus; audition-ventral and dorsal cochlear nucleus; olfaction-olfactory bulb). The systematic search yielded 91 papers (39 vision, 22 audition, 30 olfaction), revealing substantial heterogeneity in publication trends, experimental methods, measures of plasticity, and reporting across the sensory modalities. Despite these differences, commonalities emerged when correlating plasticity mechanisms with the duration of sensory deprivation. Short-term deprivation (up to 1 day) reduced activity and increased disinhibition, medium-term deprivation (1 day to a week) involved glial changes and synaptic remodelling, and long-term deprivation (over a week) primarily led to structural alterations. These findings underscore the importance of standardizing methodologies and reporting practices. Additionally, they highlight the value of cross-modals synthesis for understanding how the nervous system, including peripheral, pre-cortical, and cortical areas, respond to and compensate for sensory inputs loss. Significance Statement This study addresses the critical issue of sensory loss and its impact on the brain's adaptability, shedding light on how different sensory systems respond to loss of inputs from the environment. While past research has primarily explored early-life sensory deprivation, this study focuses on the effects of sensory loss in post-weaning rodents. By systematically reviewing 91 research articles, the findings reveal distinct responses based on the duration of sensory deprivation. This research not only enhances our understanding of brain plasticity but also has broad implications for translational applications, particularly in cross-modal plasticity, offering valuable insights into neuroscientific research and potential clinical interventions.
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.
When Camillo Golgi invented the black reaction in 1873 and first described the fine anatomical structure of the nervous system, he described a 'big nerve cell' that later took his name, the Golgi cell of cerebellum ('Golgi'schen Zellen', Gustaf Retzius, 1892). The Golgi cell was then proposed as the prototype of type-II interneurons, which form complex connections and exert their actions exclusively within the local network. Santiago Ramón y Cajal (who received the Nobel Prize with Golgi in 1906) proceeded to a detailed description of Golgi cell morphological characteristics, but functional insight remained very limited for many years. The first rediscovery happened in the 1960s, when neurophysiological analysis in vivo revealed that Golgi cells are inhibitory interneurons. This finding promoted the development of two major cerebellar theories, the 'beam theory' of John Eccles and the 'motor learning theory' of David Marr, in which the Golgi cells regulate the spatial organisation and the gain of input signals to be processed and learned by the cerebellar circuit. However, the matter was not set and a series of pioneering observations using single unit recordings and electron microscopy raised new issues that could not be fully explored until the 1990s. Then, the advent of new electrophysiological and imaging techniques in vitro and in vivo demonstrated the cellular and network activities of these neurons. Now we know that Golgi cells, through complex systems of chemical and electrical synapses, effectively control the spatio-temporal organisation of cerebellar responses. The Golgi cells regulate the timing and number of spikes emitted by granule cells and coordinate their coherent activity. Moreover, the Golgi cells regulate the induction of long-term synaptic plasticity along the mossy fibre pathway. Eventually, the Golgi cells transform the granular layer of cerebellum into an adaptable spatio-temporal filter capable of performing several kinds of logical operation. After more than a century, Golgi's intuition that the Golgi cell had to generate under a new perspective complex ensemble effects at the network level has finally been demonstrated.
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