The gradual accumulation of sensory evidence is a crucial component of perceptual decision making, but its neural mechanisms are still poorly understood. Given the wide availability of genetic and optical tools for mice, they can be useful model organisms for the study of these phenomena; however, behavioral tools are largely lacking. Here, we describe a new evidence-accumulation task for head-fixed mice navigating in a virtual reality (VR) environment. As they navigate down the stem of a virtual T-maze, they see brief pulses of visual evidence on either side, and retrieve a reward on the arm with the highest number of pulses. The pulses occur randomly with Poisson statistics, yielding a diverse yet well-controlled stimulus set, making the data conducive to a variety of computational approaches. A large number of mice of different genotypes were able to learn and consistently perform the task, at levels similar to rats in analogous tasks. They are sensitive to side differences of a single pulse, and their memory of the cues is stable over time. Moreover, using non-parametric as well as modeling approaches, we show that the mice indeed accumulate evidence: they use multiple pulses of evidence from throughout the cue region of the maze to make their decision, albeit with a small overweighting of earlier cues, and their performance is affected by the magnitude but not the duration of evidence. Additionally, analysis of the mice's running patterns revealed that trajectories are fairly stereotyped yet modulated by the amount of sensory evidence, suggesting that the navigational component of this task may provide a continuous readout correlated to the underlying cognitive variables. Our task, which can be readily integrated with state-of-the-art techniques, is thus a valuable tool to study the circuit mechanisms and dynamics underlying perceptual decision making, particularly under more complex behavioral contexts.
A primary function of the brain is to form representations of the sensory world. Its capacity to do so depends on the relationship between signal correlations, associated with neuronal receptive fields, and noise correlations, associated with neuronal response variability. It was recently shown that the behavioral relevance of sensory stimuli can modify the relationship between signal and noise correlations, presumably increasing the encoding capacity of the brain. In this work, we use data from the visual cortex of the awake mouse watching naturalistic stimuli and show that a similar modification is observed under heightened cholinergic modulation. Increasing cholinergic levels in the cortex through optogenetic stimulation of basal forebrain cholinergic neurons decreases the dependency that is commonly observed between signal and noise correlations. Simulations of correlated neural networks with realistic firing statistics indicate that this change in the correlation structure increases the encoding capacity of the network.
The basal forebrain (BF) plays crucial roles in arousal, attention, and memory, and its impairment is associated with a variety of cognitive deficits. The BF consists of cholinergic, GABAergic, and glutamatergic neurons. Electrical or optogenetic stimulation of BF cholinergic neurons enhances cortical processing and behavioral performance, but the natural activity of these cells during behavior is only beginning to be characterized. Even less is known about GABAergic and glutamatergic neurons. Here, we performed microendoscopic calcium imaging of BF neurons as mice engaged in spontaneous behaviors in their home cages (innate) or performed a go/no-go auditory discrimination task (learned). Cholinergic neurons were consistently excited during movement, including running and licking, but GABAergic and glutamatergic neurons exhibited diverse responses. All cell types were activated by overt punishment, either inside or outside of the discrimination task. These findings reveal functional similarities and distinctions between BF cell types during both spontaneous and task-related behaviors.
The dorsal pons has long been implicated in the generation of rapid eye movement (REM) sleep, but the underlying circuit mechanisms remain poorly understood. Using cell-type-specific microendoscopic Ca2+imaging in and near the laterodorsal tegmental nucleus, we found that many glutamatergic neurons are maximally active during REM sleep (REM-max), while the majority of GABAergic neurons are maximally active during wakefulness (wake-max). Furthermore, the activity of glutamatergic neurons exhibits a medio-lateral spatial gradient, with medially located neurons more selectively active during REM sleep.
The prefrontal cortex (PFC) plays a key role in controlling goal-directed behavior. Although a variety of task-related signals have been observed in the PFC, whether they are differentially encoded by various cell types remains unclear. Here we performed cellular-resolution microendoscopic Ca2+ imaging from genetically defined cell types in the dorsomedial PFC of mice performing a PFC-dependent sensory discrimination task. We found that inhibitory interneurons of the same subtype were similar to each other, but different subtypes preferentially signaled different task-related events: somatostatin-positive neurons primarily signaled motor action (licking), vasoactive intestinal peptide-positive neurons responded strongly to action outcomes, whereas parvalbumin-positive neurons were less selective, responding to sensory cues, motor action, and trial outcomes. Compared to each interneuron subtype, pyramidal neurons showed much greater functional heterogeneity, and their responses varied across cortical layers. Such cell-type and laminar differences in neuronal functional properties may be crucial for local computation within the PFC microcircuit.
The basal forebrain provides the primary source of cholinergic input to the cortex, and it plays a crucial role in promoting wakefulness and arousal. However, whether rapid changes in basal forebrain neuron spiking in awake animals can dynamically influence sensory perception is unclear. Here we show that basal forebrain cholinergic neurons rapidly regulate cortical activity and visual perception in awake, behaving mice. Optogenetic activation of the cholinergic neurons or their V1 axon terminals improved performance of a visual discrimination task on a trial-by-trial basis. In V1, basal forebrain activation enhanced visual responses and desynchronized neuronal spiking, which could partly account for the behavioral improvement. Conversely, optogenetic basal forebrain inactivation decreased behavioral performance, synchronized cortical activity and impaired visual responses, indicating the importance of cholinergic activity in normal visual processing. These results underscore the causal role of basal forebrain cholinergic neurons in fast, bidirectional modulation of cortical processing and sensory perception.
The transformation of spatial (SF) and temporal frequency (TF) tuning functions from broad-band/low-pass to narrow band-pass profiles is one of the key emergent properties of neurons in the mammalian primary visual cortex (V1). The mechanisms underlying such trans- formation are still a matter of ongoing debate. With the aim of providing comparative insights into the issue, we analyzed various aspects of the spatiotemporal tuning dynamics of neurons in the visual wulst of four awake owls. The wulst is the avian telencephalic target of the retinothalamofugal pathway and, in owls, bears striking func- tional analogy with V1. Most neurons in our sample exhibited fast and large-magnitude adaptation to the visual stimuli with response laten- cies very similar to those reported for V1. Moreover, latency in- creased as a function of stimulus SF but not TF, which suggests that parvo- and magno-like geniculate inputs could be converging onto single wulst neurons. No net shifts in preferred SF or TF were observed along the initial second of stimulation, but bandwidth decreased roughly during the first 200 ms after response latency for both stimulus dimensions. For SF, this occurred exclusively as a consequence of low-frequency suppression, whereas suppression was observed both at the low- and high-frequency limbs of TF tuning curves. Overall these results indicate that SF and TF tuning curves in the wulst are shaped by both feedforward and intratelencephalic suppressive mechanisms, similarly to what seems to be the case in the mammalian striate cortex.
The avian visual wulst is hodologically equivalent to the mammalian primary visual cortex (V1). In contrast to most birds, owls have a massive visual wulst, which shares striking functional similarities with V1. To provide a better understanding of how motion is processed within this area, we used sinusoidal gratings to characterize the spatiotemporal frequency and speed tuning profiles of 131 neurones recorded from awake burrowing owls. Cells were found to be clearly tuned to both spatial and temporal frequencies, and in a way that is similar to what has been reported in the striate cortex of primates and carnivores. Our results also suggest the presence of spatial frequency tuning domains in the wulst. Speed tuning was assessed by several methods devised to measure the degree of dependence between spatial and temporal frequency tuning. Although many neurones were found to be independently tuned, a significant proportion of cells showed at least some degree of dependence, compatible with the idea that some kind of initial transformation towards an explicit representation of speed is being carried out by the owl wulst. Interestingly, under certain constraints, a higher incidence of spatial frequency‐invariant speed tuned profiles was obtained by combining our experimentally measured responses using a recent cortical model of speed tuning. Overall, our findings reinforce the notion that, like V1, the owl wulst is an important initial stage for motion processing, a function that is usually attributed to areas of the tectofugal pathway in lateral‐eyed birds.
The avian retinothalamofugal pathway reaches the telencephalon in an area known as visual wulst. A close functional analogy between this area and the early visual cortex of mammals has been established in owls. The goal of the present study was to assess quantitatively the directional selectivity and motion integration capability of visual wulst neurones, aspects that have not been previously investigated. We recorded extracellularly from a total of 101 cells in awake burrowing owls. From this sample, 88% of the units exhibited modulated directional responses to sinusoidal gratings, with a mean direction index of 0.74 ± 0.03 and tuning bandwidth of 28 ± 1.16°. A direction index higher than 0.5 was observed in 66% of the cells, thereby qualifying them as direction selective. Motion integration was tested with moving plaids, made by adding two sinusoidal gratings of different orientations. We found that 80% of direction‐selective cells responded optimally to the motion direction of the component gratings, whereas none responded to the global motion of plaids, whose direction was intermediate to that of the gratings. The remaining 20% were unclassifiable. The strength of component motion selectivity rapidly increased over a 200 ms period following stimulus onset, maintaining a relatively sustained profile thereafter. Overall, our data suggest that, as in the mammalian primary visual cortex, the visual wulst neurones of owls signal the local orientated features of a moving object. How and where these potentially ambiguous signals are integrated in the owl brain might be important for understanding the mechanisms underlying global motion perception.