When looking around a visual scene, humans make saccadic eye movements to fixate objects of interest. While the extraocular muscles can execute saccades in any direction, not all saccade directions are equally likely: saccades in horizontal and vertical directions are most prevalent. Here, we asked whether head orientation plays a role in determining saccade direction biases. Study participants ( n  = 14) viewed natural scenes and abstract fractals (radially symmetric patterns) through a virtual reality headset equipped with eye tracking. Participants’ heads were stabilized and tilted at −30°, 0°, or 30° while viewing the images, which could also be tilted by −30°, 0°, and 30° relative to the head. To determine whether the biases in saccade direction changed with head tilt, we calculated polar histograms of saccade directions and cross-correlated pairs of histograms to find the angular displacement resulting in the maximum correlation. During free viewing of fractals, saccade biases largely followed the or...

Place code representation is ubiquitous in circuits that encode spatial parameters. For visually guided eye movements, neurons in many brain regions emit spikes when a stimulus is presented in their receptive fields and/or when a movement is directed into their movement fields. Crucially, individual neurons respond for a broad range of directions or eccentricities away from the optimal vector, making it difficult to decode the stimulus location or the saccade vector from each cell’s activity. We investigated whether it is possible to decode the spatial parameter with a population-level analysis, even when the optimal vectors are similar across neurons. Spiking activity and local field potentials (LFPs) in the superior colliculus (SC) were recorded with a laminar probe as monkeys performed a delayed saccade task to one of eight targets radially equidistant in direction. A classifier was applied offline to decode the spatial configuration as the trial progresses from sensation to action. For spiking activity...

Angular tuning is preferential sensory response to a directional stimulus and is observed in the whisker tactile system. In whisker hair follicles, there are at least three types of low threshold mechanoreceptors (LTMRs): rapidly adapting (RA), slowly adapting type 1 (SA1), and slowly adapting type 2 (SA2). These LTMRs display angular tuning but their properties remain incompletely studied. Here, we used isolated rat whisker hair follicles and pressure-clamped single-fiber recordings to study angular tuning of these LTMRs. Angular tuning was determined with impulses elicited by ramp-and-hold deflection of whisker hair in 24 directions each at 15° for a total of 360°. We show that RA display impulses during ramp-up, both ramp-up and ramp-down, or ramp-down dynamic phases. Both SA1 and SA2 respond to angular stimuli with slowly adapting impulses in most angles. However, SA1 and SA2 show rapidly adapting responses in other angles. All the three types of LTMRs display strong angular tuning, and there is no sig...

The ability of humans to coordinate stereotyped, alternating movements between the two legs during bipedal walking is a complex motor behavior that requires precisely timed activities across multiple nodes of the supraspinal network. Understanding of the neural network dynamics that underlie natural walking in humans is limited. We investigated cortical and subthalamic neural activities during overground walking and evaluated spectral biomarkers to decode the gait cycle in three patients with Parkinson’s disease without gait disturbances. Patients were implanted with chronic bilateral deep brain stimulation (DBS) leads in the subthalamic nucleus (STN) and electrocorticography paddles overlaying the primary motor and somatosensory cortices. Local field potentials were recorded from these areas while the participants performed overground walking and synchronized to external gait kinematic sensors. We found that the STN displays increased low-frequency (4–12 Hz) spectral power during the period before contral...

Absence of presynaptic protein MUNC18-1 (gene: Stxbp1 ) leads to neuronal cell death at an immature stage before synapse formation. Here, we performed transcriptomic and proteomic profiling of immature Stxbp1 knock-out (KO) cells to discover which cellular processes depend on MUNC18-1. Hippocampi of Stxbp1 KO mice showed cell type-specific dysregulation of 2123 transcripts primarily related to synaptic transmission and immune response. To further investigate direct, neuron-specific effects of MUNC18-1 depletion, a proteomic screen was performed on murine neuronal cultures at two developmental timepoints before onset of neuron degeneration. 399 proteins were differentially expressed, which were primarily involved in synaptic function (especially synaptic vesicle exocytosis) and neuron development. We further show that many of the downregulated proteins on loss of MUNC18-1 are normally upregulated during this developmental stage. Thus, absence of MUNC18-1 extensively dysregulates the transcriptome and proteo...

Successful retrieval of a specific item from visual working memory (VWM) depends on the binding of that item to its unique context. Recent functional magnetic resonance imaging studies of VWM manipulating memory set homogeneity have identified an important role for the intraparietal sulcus in context binding, independent of any role in representing stimulus identity. The current study explored whether the contralateral delay activity (CDA), which is an event-related potential (ERP) component derived from posterior electrodes that tracks the amount of information held in VWM, might also be sensitive to context-binding demands. In experiment 1, human participants performed lateralized delayed recognition with memory sets containing one, three, or five items that were drawn from the same category (orientations: “homogeneous”) or from different categories (orientation, color, and luminance: “heterogeneous”). Because the location and identity of the memory probe indicated the item to be retrieved, homogeneous t...

Adaptive control is the online adjustment of behavior to guide and optimize responses after errors or conflict. The neural circuits involved in monitoring and adapting behavioral performance following error are poorly understood. The prefrontal cortex (PFC) plays a critical role in this form of control. However, these brain areas are densely connected with many other regions, and it is unknown which projections are critical for adaptive behavior. Here, we tested the involvement of four distinct dorsal and ventral prefrontal cortical projections to striatal and thalamic target areas in adaptive control. We re-analyzed data from published experiments, using trial-by-trial analyses of behavior in an operant task for attention and impulsivity. We find that male rats slow their responses and perform worse following errors. Moreover, by combining retrograde labeling and chemogenetic silencing, we find that dorsomedial prefrontal pyramidal neurons that project to the lateral nucleus of the mediodorsal thalamus (M...

Primary sensory cortices display functional topography, suggesting that even small cortical volumes may underpin perception of specific stimuli. Traditional loss-of-function approaches have a relatively large radius of effect (>1 mm) and few studies track recovery following loss-of-function perturbations. Consequently, the behavioral necessity of smaller cortical volumes remains unclear. In the mouse primary vibrissal somatosensory cortex (vS1), ‘barrels’ with a radius of ∼150 μm receive input predominantly from a single whisker, partitioning vS1 into a topographic map of well-defined columns. Here, we train animals implanted with a cranial window over vS1 to perform single-whisker perceptual tasks. We then use high-power laser exposure centered on the barrel representing the spared whisker to produce lesions with a typical volume of 1-2 barrels. These columnar-scale lesions impair performance in an object location discrimination task for multiple days without disrupting vibrissal kinematics. Animals with ...

Brain-derived neurotrophic factor (BDNF) is a widely expressed neurotrophin that supports the survival, differentiation and signaling of various neuronal populations. Although it has been well described that expression of BDNF is strongly regulated by neuronal activity, little is known whether regulation of BDNF expression is similar in different brain regions. Here, we focused on this fundamental question using neuronal populations obtained from rat cerebral cortices and hippocampi of both sexes. First, we thoroughly characterized the role of the best-described regulators of BDNF gene – CREB family transcription factors, and show that activity-dependent BDNF expression depends more on CREB and the coactivators CBP and CRTC1 in cortical than in hippocampal neurons. Our data also reveal an important role of CREB in the early induction of BDNF mRNA expression after neuronal activity and only modest contribution after prolonged neuronal activity. We further corroborated our findings at BDNF protein level. To ...

Neurons express overlapping homeostatic mechanisms to regulate synaptic function and network properties in response to perturbations of neuronal activity. Endocannabinoids (eCBs) are bioactive lipids synthesized in the post-synaptic compartments to regulate synaptic transmission, plasticity, and neuronal excitability primarily through retrograde activation of pre-synaptic cannabinoid receptor type 1 (CB1). The eCB system is well-situated to regulate neuronal network properties and coordinate pre- and post-synaptic activity. However, the role of the eCB system in homeostatic adaptations to neuronal hyperactivity is unknown. To address this issue, we used western blot and targeted lipidomics to measure adaptations in eCB system to bicuculline (BCC)-induced chronic hyperexcitation in mature (>DIV21) cultured rat cortical neurons, and used multielectrode array recording and live-cell imaging of glutamate dynamics to test the effects of pharmacological manipulations of eCB on network activities. We show that BC...