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The superior colliculus (SC) is a midbrain structure that plays a central role in visual processing. Although we have learned a considerable amount about the function of single SC neurons, the way in which sensory information is represented and processed on the population level in awake behaving animals and across a large region of the retinotopic map is still largely unknown. Partially because the SC is anatomically located below the cortical sheet and the transverse sinus, it is technically difficult to measure neuronal activity from a large population of neurons in SC. To address this, we propose a tangential recording configuration using high-density electrode probes (Neuropixels) in mouse SC in vivo that permits a large number of recording sites (~200) accessibility inside the SC circuitry. This approach thereby provides a unique opportunity to measure the activity of SC neuronal populations composing up to ~2 mm of SC tissue and characterized by receptive fields covering an extended region in the visual field. Here we describe how to perform tangential recordings along the anterior-posterior and the medio-lateral axis of the mouse SC in vivo and how to combine this approach with optogenetic tools for cell-type identification on the population level.

Navigation through complex environments requires motor planning, motor preparation and the coordination between multiple sensory–motor modalities. For example, the stepping motion when we walk is coordinated with motion of the torso, arms, head and eyes. In rodents, movement of the animal through the environment is often coordinated with whisking. Here we trained head fixed mice – navigating a floating Airtrack plus maze – to overcome their directional preference and use cues indicating the direction of movement expected in each trial. Once cued, mice had to move backward out of a lane, then turn in the correct direction, and enter a new lane. In this simple paradigm, as mice begin to move backward, they position their whiskers asymmetrically: whiskers on one side of the face protract, and on the other side they retract. This asymmetry reflected the turn direction. Additionally, on each trial, mice move their eyes conjugately in the direction of the upcoming turn. Not only do they move their eyes, but saccadic eye movement is coordinated with the asymmetric positioning of the whiskers. Our analysis shows that the asymmetric positioning of the whiskers predicts the direction of turn that mice will make at an earlier stage than eye movement does. We conclude that, when mice move or plan to move in complex real-world environments, their motor plan and behavioral state can be read out in the movement of both their whiskers and eyes.Significance statementNatural behavior occurs in multiple sensory and motor dimensions. When we move through our environment we coordinate the movement of our body, head, eyes and limbs. Here we show that when mice navigate a maze, they move their whiskers and eyes; they position their whiskers asymmetrically, and use saccadic eye movements. The position of the eyes and whiskers predicts the direction mice will turn in. This work suggests that when mice move through their environment, they coordinate the visual-motor and somatosensory-motor systems.

Excitatory synaptic input reaches the soma of a cortical excitatory pyramidal neuron via anatomically segregated apical and basal dendrites. In vivo, dendritic inputs are integrated during depolarized network activity, but how network activity affects apical and basal inputs is not understood. Using subcellular two-photon stimulation of Channelrhodopsin2-expressing layer 2/3 pyramidal neurons in somatosensory cortex, nucleus-specific thalamic optogenetic stimulation, and paired recordings, we show that slow, depolarized network activity amplifies small-amplitude synaptic inputs targeted to basal dendrites but reduces the amplitude of all inputs from apical dendrites and the cell soma. Intracellular pharmacology and mathematical modeling suggests that the amplification of weak basal inputs is mediated by postsynaptic voltage-gated channels. Thus, network activity dynamically reconfigures the relative somatic contribution of apical and basal inputs and could act to enhance the detectability of weak synaptic inputs.

A defining feature of cortical layer 2/3 excitatory neurons is their sparse activity, often firing in singlets of action potentials. Local inhibitory neurons are thought to play a major role in regulating sparseness, but which cell types are recruited by single excitatory synaptic inputs is unknown. Using multiple, targeted, in vivo whole-cell recordings, we show that single EPSPs have little effect on the firing rates of excitatory neurons and somatostatin-expressing GABA-ergic inhibitory neurons but evoke precisely timed action potentials in parvalbumin-expressing inhibitory neurons. Despite a EPSP decay time of 7.8 ms, the evoked action potentials were almost completely restricted to the EPSP rising phase (~0.5 ms). Evoked parvalbumin-expressing neuron action potentials go on to inhibit the local excitatory network, thus providing a pathway for single spike evoked disynaptic inhibition which may enforce sparse and precisely timed cortical signaling.

The synchronized activity of six layers of cortical neurons is critical for sensory perception and the control of voluntary behavior, but little is known about the synaptic mechanisms of cortical synchrony across layers in behaving animals. We made single and dual whole-cell recordings from the primary somatosensory forepaw cortex in awake mice and show that L2/3 and L5 excitatory neurons have layer-specific intrinsic properties and membrane potential dynamics that shape laminar-specific firing rates and subthreshold synchrony. First, while sensory and movement-evoked synaptic input was tightly correlated across layers, spontaneous action potentials and slow spontaneous subthreshold fluctuations had laminar-specific timing; second, longer duration forepaw movement was associated with a decorrelation of subthreshold activity; third, spontaneous and sensory-evoked forepaw movements were signaled more strongly by L5 than L2/3 neurons. Together, our data suggest that the degree of translaminar synchrony is dependent upon the origin (sensory, spontaneous, and movement) of the synaptic input.

Little is known about the properties of monosynaptic connections between identified neurons in vivo. We made multiple (two to four) two-photon targeted whole-cell recordings from neighboring layer 2 mouse somatosensory barrel cortex pyramidal neurons in vivo to investigate excitatory monosynaptic transmission in the hyperpolarized downstate. We report that pyramidal neurons form a sparsely connected (6.7% connectivity) network with an overrepresentation of bidirectional connections. The majority of unitary excitatory postsynaptic potentials were small in amplitude (1 mV. The coefficient of variation (CV = 0.74) could largely be explained by the presence of synaptic failures (22%). Both the CV and failure rates were reduced with increasing amplitude. The mean paired-pulse ratio was 1.15 and positively correlated with the CV. Our approach will help bridge the gap between connectivity and function and allow investigations into the impact of brain state on monosynaptic transmission and integration.