Topic: two-photon calcium imaging

Recent advances in techniques for monitoring and perturbing neural populations have greatly enhanced our ability to study circuits in the brain. In particular, two-photon holographic optogenetics now enables precise photostimulation of experimenter-specified groups of individual neurons, while simultaneous two-photon calcium imaging enables the measurement of ongoing and induced activity across the neural population. Despite the enormous space of potential photostimulation patterns and the time-consuming nature of photostimulation experiments, very little algorithmic work has been done to dete

Cognitive maps confer animals with flexible intelligence by representing spatial, temporal, and abstract relationships that can be used to shape thought, planning, and behavior. Cognitive maps have been observed in the hippocampus, but their algorithmic form and the processes by which they are learned remain obscure. Here, we employed large-scale, longitudinal two-photon calcium imaging to record activity from thousands of neurons in the CA1 region of the hippocampus while mice learned to efficiently collect rewards from two subtly different versions of linear tracks in virtual reality. The r

Pyramidal neurons have apical dendrites that are both physically and electrically segregated from their cell bodies. In sensory cortex, these apical dendrites receive primarily top-down signals from associative and motor regions, while the cell bodies and nearby dendrites of these same pyramidal neurons are mostly targeted by bottom-up or locally recurrent inputs from the sensory periphery. Due to these differences, a number of theories in computational neuroscience postulate a unique role for apical dendrites in shaping sensory processing and plasticity in the face of new or surprising stimul

Stringer et al. used two-photon calcium imaging to record activity from tens of thousands of V1 cells in head-fixed mice during a visual orientation discrimination task, and showed that the neural response encodes stimulus discrimination thresholds nearly 100 times more precise than the corresponding behavioral thresholds. Animal arousal state was monitored by measuring the locomotion speed during task execution, but could not explain this large discrepancy in discrimination threshold. Here, we take advantage of the fact that the behavioral data was acquired in that experiment, and ask whethe

Cells preferentially responding to visual motion in a particular direction are said to be direction-selective, and these were first identified in the primary visual cortex. Since then, direction-selective responses have been observed in the retina of several species, including mice, indicating motion analysis begins at the earliest stage of the visual hierarchy. Yet little is known about how retinal direction selectivity contributes to motion processing in the visual cortex. In this talk, I will present our experimental efforts to narrow this gap in our knowledge. To this end, we used genetic

How the brain stores a sequence in memory remains largely unknown. We investigated the neural code underlying sequence working memory using two-photon calcium imaging to record thousands of neurons in the prefrontal cortex of macaque monkeys memorizing and then reproducing a sequence of locations after a delay. We discovered a regular geometrical organization: The high-dimensional neural state space during the delay could be decomposed into a sum of low-dimensional subspaces, each storing the spatial location at a given ordinal rank, which could be generalized to novel sequences and explain mo

Large-scale recordings of neural activity are providing new opportunities to study network-level dynamics with unprecedented detail. However, the sheer volume of data and its dynamical complexity are major barriers to uncovering and interpreting these dynamics. I will present machine learning frameworks that enable inference of dynamics from neuronal population spiking activity on single trials and millisecond timescales, from diverse brain areas, and without regard to behavior. I will then demonstrate extensions that allow recovery of dynamics from two-photon calcium imaging data with surpris

Tracking heading within an environment is a fundamental requirement for flexible, goal-directed navigation. In insects, a head-direction representation that guides the animal’s movements is maintained in a conserved brain region called the central complex. Two-photon calcium imaging of genetically targeted neural populations in the central complex of tethered fruit flies behaving in virtual reality (VR) environments has shown that the head-direction representation is updated based on self-motion cues and external sensory information, such as visual features and wind direction. Thus far, the he

At any given moment the brain receives more sensory information than it can use to guide adaptive behaviour, creating the need for mechanisms that promote efficient processing of incoming sensory signals. One way in which the brain might reduce its sensory processing load is to encode successive presentations of the same stimulus in a more efficient form, a process known as neural adaptation. Conversely, when a stimulus violates an expected pattern, it should evoke an enhanced neural response. Such a scheme for sensory encoding has been formalised in predictive coding theories, which propose t

Starting with the work of Hodgkin and Huxley in the 1950s, we now have a fairly good understanding of how the spiking activity of neurons can be modelled mathematically. For cortical circuits the understanding is much more limited. Most network studies have considered stylized models with a single or a handful of neuronal populations consisting of identical neurons with statistically identical connection properties. However, real cortical networks have heterogeneous neural populations and much more structured synaptic connections. Unlike typical simplified cortical network models, real network

The analysis of neuronal ensembles often suffers from low spiking activity. As statistical analysis relies on sufficiently large samples, rare joint events in neuronal ensembles usually fail to reach statistical significance. We show that statistical power can be enhanced considerably by careful preselection of specific, separated temporal stripes distributed throughout the whole time series in which spiking is more likely to occur. In a data set of two-photon calcium imaging from the visual cortex of mice (Cleppien et al., 2024+), we identified short temporal stripes of interest from the un

The hippocampus (HC) plays a pivotal role in spatial navigation and memory in the human brain. Place cells, specialised neurons residing within the hippocampus, exhibit selective firing patterns corresponding to specific spatial locations, collectively contributing to the cognitive mapping of the environment. In healthy state, the place fields in the CA1 region exhibits continuous representational turnover [1]. Spatial navigation is disrupted in Alzheimer’s Disease (AD). AD, a neurodegenerative disorder characterised by progressive cognitive decline, is associated with deficits in learning a