The cerebellum Carey, Megan R
CB/Current biology,
01/2024, Volume:
34, Issue:
1
Journal Article
Peer reviewed
Open access
The cerebellum, that stripey 'little brain', sits at the back of your head, under your visual cortex, and contains more than half of the neurons in your entire nervous system. The cerebellum is ...highly conserved across vertebrates, and its evolutionary expansion has tended to proceed in concert with expansion of cerebral cortex. The crystalline neuronal architecture of the cerebellar cortex was first described by Cajal a century ago, and its functional connectivity was elucidated in exquisite anatomical and physiological detail by the mid-20
century. The ability to clearly identify molecularly distinct cerebellar cell types that constitute discrete circuit elements is perhaps unparalleled among brain areas, even within the context of modern circuit neuroscience. Although traditionally thought of as primarily a motor structure, the cerebellum is highly interconnected with diverse brain areas and, as I will explain in this Primer, is well-poised to influence a wide range of motor and cognitive functions.
Stable and efficient locomotion requires the precise coordination of movement across the limbs and body. Learned changes in interlimb coordination can be induced by exposure to a split-belt treadmill ...that imposes different speeds under each side of the body. Here, we demonstrate locomotor learning on a split-belt treadmill in mice. Mouse locomotor adaptation is specific to measures of interlimb coordination, has spatial and temporal components that adapt at different rates, and is context specific. The many similarities between human and mouse locomotor adaptation suggest that this form of locomotor learning is highly conserved across vertebrates. Using a variety of approaches, we demonstrate that split-belt adaptation in mice specifically depends on the intermediate cerebellum but is insensitive to large lesions of the cerebral cortex. Finally, cell-type-specific chemogenetics combined with quantitative behavioral analysis reveals that spatial and temporal components of locomotor adaptation are dissociable on the circuit level.
Display omitted
•Locomotor learning on a split-belt treadmill is highly conserved across vertebrates•Mice regain gait symmetry by calibrating interlimb coordination in space and time•Locomotor adaptation requires intermediate cerebellum but not cerebral cortex•Circuit mechanisms for spatial and temporal components of learning are dissociable
Darmohray et al. describe a rapid form of cerebellum-dependent locomotor learning in mice that appears to be highly conserved across vertebrates. Cell-type-specific chemogenetics combined with quantitative behavioral analysis reveals that mechanisms for spatial and temporal components of learning are dissociable on the circuit level.
The COVID-19 pandemic has posed major challenges for diversity, equity, and inclusion (DEI) efforts in research and academia. As chairs of the ALBA Network, we reflect on how the pandemic has ...exacerbated, and also shone a spotlight on, inequalities in science and society.
The COVID-19 pandemic has posed major challenges for diversity, equity, and inclusion (DEI) efforts in research and academia. As chairs of the ALBA Network, Sandi and Carey reflect on how the pandemic has exacerbated, and also shone a spotlight on, inequalities in science and society.
Changes in behavioral state can profoundly influence brain function. Here we show that behavioral state modulates performance in delay eyeblink conditioning, a cerebellum-dependent form of ...associative learning. Increased locomotor speed in head-fixed mice drove earlier onset of learning and trial-by-trial enhancement of learned responses that were dissociable from changes in arousal and independent of sensory modality. Eyelid responses evoked by optogenetic stimulation of mossy fiber inputs to the cerebellum, but not at sites downstream, were positively modulated by ongoing locomotion. Substituting prolonged, low-intensity optogenetic mossy fiber stimulation for locomotion was sufficient to enhance conditioned responses. Our results suggest that locomotor activity modulates delay eyeblink conditioning through increased activation of the mossy fiber pathway within the cerebellum. Taken together, these results provide evidence for a novel role for behavioral state modulation in associative learning and suggest a potential mechanism through which engaging in movement can improve an individual's ability to learn.
Highlights ► Synapses throughout the cerebellum exhibit long-term plasticity. ► In vivo whole cell recordings provide glimpses into granule cell sensory processing. ► Multiple forms of plasticity at ...parallel fiber synapses interact in unexpected ways. ► Mossy fiber synapses in the deep cerebellar nuclei are bidirectionally plastic. ► Understanding how diverse plasticity mechanisms work together to support learning is a current goal.
Antimicrobial resistance (AMR) is a major global public health threat, which has been largely driven by the excessive use of antimicrobials. Control measures are urgently needed to slow the ...trajectory of AMR but are hampered by an incomplete understanding of the interplay between pathogens, AMR encoding genes, and mobile genetic elements at a microbial level. These factors, combined with the human, animal, and environmental interactions that underlie AMR dissemination at a population level, make for a highly complex landscape. Whole-genome sequencing (WGS) and, more recently, metagenomic analyses have greatly enhanced our understanding of these processes, and these approaches are informing mitigation strategies for how we better understand and control AMR. This review explores how WGS techniques have advanced global, national, and local AMR surveillance, and how this improved understanding is being applied to inform solutions, such as novel diagnostic methods that allow antimicrobial use to be optimised and vaccination strategies for better controlling AMR. We highlight some future opportunities for AMR control informed by genomic sequencing, along with the remaining challenges that must be overcome to fully realise the potential of WGS approaches for international AMR control.
Momentum for achieving widespread control of typhoid fever has been growing over the past decade. Typhoid conjugate vaccines represent a potentially effective tool to reduce the burden of disease in ...the foreseeable future and new data have recently emerged to better frame their use-case.
We describe how antibiotic resistance continues to pose a major challenge in the treatment of typhoid fever, as exemplified by the emergence of azithromycin resistance and the spread of Salmonella Typhi strains resistant to third-generation cephalosporins. We review efficacy and effectiveness data for TCVs, which have been shown to have high-level efficacy (≥80%) against typhoid fever in diverse field settings. Data from randomized controlled trials and observational studies of TCVs are reviewed herein. Finally, we review data from multicountry blood culture surveillance studies that have provided granular insights into typhoid fever epidemiology. These data are becoming increasingly important as countries decide how best to introduce TCVs into routine immunization schedules and determine the optimal delivery strategy.
Continued advocacy is needed to address the ongoing challenge of typhoid fever to improve child health and tackle the rising challenge of antimicrobial resistance.
PDF
