Behind mouse eyes: The function and control of eye movements in mice.

The mouse visual system has become the most popular model to study the cellular and circuit mechanisms of sensory processing. However, the importance of eye movements only started to be appreciated recently. Eye movements provide a basis for predictive sensing and deliver insights into various brain functions and dysfunctions.

RPM: An open-source Rotation Platform for open- and closed-loop vestibular stimulation in head-fixed Mice.

Head fixation allows the recording and presentation of controlled stimuli and is used to study neural processes underlying spatial navigation. However, it disrupts the head direction system because of the lack of vestibular stimulation. To overcome this limitation, we developed a novel rotation platform which can be driven by the experimenter (open-loop) or by animal movement (closed-loop).

Quantitative analysis of rabies virus-based synaptic connectivity tracing.

Monosynaptically restricted rabies viruses have been used for more than a decade for synaptic connectivity tracing. However, the verisimilitude of quantitative conclusions drawn from these experiments is largely unknown. The primary reason is the simple metrics commonly used, which generally disregard the effect of starter cell numbers.

Dendritic Domain-Specific Sampling of Long-Range Axons Shapes Feedforward and Feedback Connectivity of L5 Neurons.

Feedforward and feedback pathways interact in specific dendritic domains to enable cognitive functions such as predictive processing and learning. Based on axonal projections, hierarchically lower areas are thought to form synapses primarily on dendrites in middle cortical layers, whereas higher-order areas are thought to target dendrites in layer 1 and in deep layers. However, the extent to which functional synapses form in regions of axodendritic overlap has not been extensively studied.

jULIEs: nanostructured polytrodes for low traumatic extracellular recordings and stimulation in the mammalian brain.

Extracellular microelectrode techniques are the most widely used approach to interrogate neuronal populations. However, regardless of the manufacturing method used, damage to the vasculature and circuit function during probe insertion remains a concern. This issue can be mitigated by minimising the footprint of the probe used.

Apical length governs computational diversity of layer 5 pyramidal neurons.

Anatomical similarity across the neocortex has led to the common assumption that the circuitry is modular and performs stereotyped computations. Layer 5 pyramidal neurons (L5PNs) in particular are thought to be central to cortical computation because of their extensive arborisation and nonlinear dendritic operations. Here, we demonstrate that computations associated with dendritic Ca plateaus in mouse L5PNs vary substantially between the primary and secondary visual cortices.

Widespread vestibular activation of the rodent cortex.

Much of our understanding of the neuronal mechanisms of spatial navigation is derived from chronic recordings in rodents in which head-direction, place, and grid cells have all been described. However, despite the proposed importance of self-reference information to these internal representations of space, their congruence with vestibular signaling remains unclear. Here we have undertaken brain-wide functional mapping using both fMRI and electrophysiological methods to directly determine the spatial extent, strength, and time course of vestibular signaling across the rat forebrain.

The stimulus selectivity and connectivity of layer six principal cells reveals cortical microcircuits underlying visual processing.

Sensory computations performed in the neocortex involve layer six (L6) cortico-cortical (CC) and cortico-thalamic (CT) signaling pathways. Developing an understanding of the physiological role of these circuits requires dissection of the functional specificity and connectivity of the underlying individual projection neurons. By combining whole-cell recording from identified L6 principal cells in the mouse primary visual cortex (V1) with modified rabies virus-based input mapping, we have determined the sensory response properties and upstream monosynaptic connectivity of cells mediating the CC or CT pathway.

A biophysical signature of network affiliation and sensory processing in mitral cells.

One defining characteristic of the mammalian brain is its neuronal diversity. For a given region, substructure, layer or even cell type, variability in neuronal morphology and connectivity persists. Although it is well known that such cellular properties vary considerably according to neuronal type, the substantial biophysical diversity of neurons of the same morphological class is typically averaged out and ignored.

Transfection via whole-cell recording in vivo: bridging single-cell physiology, genetics and connectomics.

Single-cell genetic manipulation is expected to substantially advance the field of systems neuroscience. However, existing gene delivery techniques do not allow researchers to electrophysiologically characterize cells and to thereby establish an experimental link between physiology and genetics for understanding neuronal function. In the mouse brain in vivo, we found that neurons remained intact after 'blind' whole-cell recording, that DNA vectors could be delivered through the patch-pipette during such recordings and that these vectors drove protein expression in recorded cells for at least 7 d.

Dendritic spikes mediate negative synaptic gain control in cerebellar Purkinje cells.

Dendritic spikes appear to be a ubiquitous feature of dendritic excitability. In cortical pyramidal neurons, dendritic spikes increase the efficacy of distal synapses, providing additional inward current to enhance axonal action potential (AP) output, thus increasing synaptic gain. In cerebellar Purkinje cells, dendritic spikes can trigger synaptic plasticity, but their influence on axonal output is not well understood.

Dendritic excitability and synaptic plasticity.

Most synaptic inputs are made onto the dendritic tree. Recent work has shown that dendrites play an active role in transforming synaptic input into neuronal output and in defining the relationships between active synapses. In this review, we discuss how these dendritic properties influence the rules governing the induction of synaptic plasticity.

High-fidelity transmission of sensory information by single cerebellar mossy fibre boutons.

Understanding the transmission of sensory information at individual synaptic connections requires knowledge of the properties of presynaptic terminals and their patterns of firing evoked by sensory stimuli. Such information has been difficult to obtain because of the small size and inaccessibility of nerve terminals in the central nervous system. Here we show, by making direct patch-clamp recordings in vivo from cerebellar mossy fibre boutons-the primary source of synaptic input to the cerebellar cortex-that sensory stimulation can produce bursts of spikes in single boutons at very high instantaneous firing frequencies (more than 700 Hz).

Dendritic patch-clamp recording.

The patch-clamp technique allows investigation of the electrical excitability of neurons and the functional properties and densities of ion channels. Most patch-clamp recordings from neurons have been made from the soma, the largest structure of individual neurons, while their dendrites, which form the majority of the surface area and receive most of the synaptic input, have been relatively neglected. This protocol describes techniques for recording from the dendrites of neurons in brain slices under direct visual control.

Dendritic calcium spikes are tunable triggers of cannabinoid release and short-term synaptic plasticity in cerebellar Purkinje neurons.

Understanding the relationship between dendritic excitability and synaptic plasticity is vital for determining how dendrites regulate the input-output function of the neuron. Dendritic calcium spikes have been associated with the induction of long-term changes in synaptic efficacy. Here we use direct recordings from cerebellar Purkinje cell dendrites to show that synaptically activated local dendritic calcium spikes are potent triggers of cannabinoid release, producing a profound and short-term reduction in synaptic efficacy at parallel fiber synapses.