Neuronal activity patterns in microcircuits of the cerebellar cortical C3 zone during reaching.

The cerebellum is the largest sensorimotor structure in the brain. A fundamental organizational feature of its cortex is its division into a series of rostrocaudally elongated zones. These are defined by their inputs from specific parts of the inferior olive and Purkinje cell output to specific cerebellar and vestibular nuclei. However, little is known about how patterns of neuronal activity in zones, and their microcircuit subdivisions, microzones, are related to behaviour in awake animals. In the present study, we investigated the organization of microzones within the C3 zone and their activity during a skilled forelimb reaching task in cats. Neurons in different microzones of the C3 zone, functionally determined by receptive field characteristics, differed in their patterns of activity during movement. Groups of Purkinje cells belonging to different receptive field classes, and therefore belonging to different microzones, were found to collectively encode different aspects of the reach controlled by the C3 zone. Our results support the hypothesis that the cerebellar C3 zone is organized and operates within a microzonal frame of reference, with a specific relationship between the sensory input to each microzone and its motor output. KEY POINTS: A defining feature of cerebellar organization is its division into a series of zones and smaller subunits termed microzones. Much of how zones and microzones are organized has been determined in anaesthetized preparations, and little is known about their function in awake animals. We recorded from neurons in the forelimb part of the C3 zone 'in action' by recording from single cerebellar cortical neurons located in different microzones defined by their peripheral receptive field properties during a forelimb reach-retrieval task in cats. Neurons from individual microzones had characteristic patterns of activity during movement, indicating that function is organized in relation to microcomplexes.

Gut microbiome effects on neuronal excitability & activity: Implications for epilepsy.

It is now well established that the bacterial population of the gastrointestinal system, known as the gut microbiome, is capable of influencing the brain and its dependent functions. Links have been demonstrated between the microbiome and a variety of normal and pathological neural functions, including epilepsy. Many of these microbiome-brain links involve the direct or indirect modulation of the excitability and activity of individual neurons by the gut microbiome. Such links may be particularly significant when it comes to microbiome modulation of epilepsy, often considered a disorder of neuronal excitability. In this review we consider the current evidence of a relationship between the gut microbiome and the excitability or activity of neurons in the context of epilepsy. The review focuses particularly on evidence of direct, causal microbiome effects on neuronal excitability or activity, but also considers demonstrations of microbiome to host interactions that are likely to have an indirect influence. While we identify a few common themes, it is apparent that deriving general mechanistic principles of microbiome influence on these parameters in epilepsy will require considerable further study to tease out the many interacting factors, systems, and conditions.

Microbial memories: Sex-dependent impact of the gut microbiome on hippocampal plasticity.

Germ-free rodents, raised in the absence of a measurable gut microbiome, have been a key model to study the microbiome-gut-brain axis. Germ-free mice exhibit marked behavioural and neurochemical differences to their conventionally raised counterparts. It is as yet unclear how these neurochemical differences lead to the behavioural differences. Here, we test the electrophysiological properties of hippocampal plasticity in adult germ-free mice and compare them to conventionally raised counterparts. Whilst basal synaptic efficacy and pre-synaptic short-term plasticity appear normal, we find a striking alteration of hippocampal long-term potentiation specifically in male germ-free slices. However, the spike output of these neurons remains normal along with altered input-output coupling, potentially indicating homeostatic compensatory mechanisms, or an altered excitation/inhibition balance. To our knowledge this is the first time the electrophysiological properties of the hippocampus have been assessed in a microbiome deficient animal. Our data indicate that the absence of a microbiome alters integration of dendritic signalling in the CA1 region in mice.

Pre-movement changes in sensorimotor beta oscillations predict motor adaptation drive.

Beta frequency oscillations in scalp electroencephalography (EEG) recordings over the primary motor cortex have been associated with the preparation and execution of voluntary movements. Here, we test whether changes in beta frequency are related to the preparation of adapted movements in human, and whether such effects generalise to other species (cat). Eleven healthy adult humans performed a joystick visuomotor adaptation task. Beta (15-25 Hz) scalp EEG signals recorded over the motor cortex during a pre-movement preparatory phase were, on average, significantly reduced in amplitude during early adaptation trials compared to baseline, late adaptation, or aftereffect trials. The changes in beta were not related to measurements of reaction time or reach duration. We also recorded local field potential (LFP) activity within the primary motor cortex of three cats during a prism visuomotor adaptation task. Analysis of these signals revealed similar reductions in motor cortical LFP beta frequencies during early adaptation. This effect was present when controlling for any influence of the reaction time and reach duration. Overall, the results are consistent with a reduction in pre-movement beta oscillations predicting an increase in adaptive drive in upcoming task performance when motor errors are largest in magnitude and the rate of adaptation is greatest.