Calcium Imaging of Basal Forebrain Activity during Innate and Learned Behaviors.

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.

Re-Establishment of Cortical Motor Output Maps and Spontaneous Functional Recovery via Spared Dorsolaterally Projecting Corticospinal Neurons after Dorsal Column Spinal Cord Injury in Adult Mice.

Unlabelled: Motor cortical plasticity contributes to spontaneous recovery after incomplete spinal cord injury (SCI), but the pathways underlying this remain poorly understood. We performed optogenetic mapping of motor cortex in channelrhodopsin-2 expressing mice to assess the capacity of the cortex to re-establish motor output longitudinally after a C3/C4 dorsal column SCI that bilaterally ablated the dorsal corticospinal tract (CST) containing ∼96% of corticospinal fibers but spared ∼3% of CST fibers that project via the dorsolateral funiculus. Optogenetic mapping revealed extensive early deficits, but eventual reestablishment of motor cortical output maps to the limbs at the same latency as preoperatively by 4 weeks after injury.

Motor maps and the cortical control of movement.

The brain's cortical maps serve as a macroscopic framework upon which additional levels of detail can be overlaid. Unlike sensory maps generated by measuring the brain's responses to incoming stimuli, motor maps are made by directly stimulating the brain itself. To understand the significance of motor maps and the functions they represent, it is necessary to consider the relationship between the natural operation of the motor system and the pattern of activity evoked in it by artificial stimulation.

Ministrokes in channelrhodopsin-2 transgenic mice reveal widespread deficits in motor output despite maintenance of cortical neuronal excitability.

We evaluated the effects of ministrokes targeted to individual pial arterioles on motor function in Thy-1 line 18 channelrhodopsin-2 (ChR2) transgenic mice within the first hours after ischemia. Using optogenetics, we directly assessed both the excitability and motor output of cortical neurons in a manner independent of behavioral state or training. Occlusion of individual arterioles within the motor cortex led to a ministroke that was verified using laser speckle contrast imaging.

Fast modulation of visual perception by basal forebrain cholinergic neurons.

The basal forebrain provides the primary source of cholinergic input to the cortex, and it has a crucial function 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.

Displacement of sensory maps and disorganization of motor cortex after targeted stroke in mice.

Background And Purpose: Recovery from stroke is hypothesized to involve the reorganization of surviving cortical areas. To study the functional organization of sensorimotor cortex at multiple time points before and after stroke, we performed longitudinal light-based motor mapping of transgenic mice expressing light-sensitive channelrhodopsin-2 in layer 5 cortical neurons.

Methods: Pulses of light stimulation were targeted to an array of cortical points, whereas evoked forelimb motor activity was recorded using noninvasive motion sensors.

Towards a circuit mechanism for movement tuning in motor cortex.

The firing rates of neurons in primate motor cortex have been related to multiple parameters of voluntary movement. This finding has been corroborated by stimulation-based studies that have mapped complex movements in rodent and primate motor cortex. However, it has been difficult to link the movement tuning of a neuron with its role within the cortical microcircuit.

Distinct cortical circuit mechanisms for complex forelimb movement and motor map topography.

Cortical motor maps are the basis of voluntary movement, but they have proven difficult to understand in the context of their underlying neuronal circuits. We applied light-based motor mapping of Channelrhodopsin-2 mice to reveal a functional subdivision of the forelimb motor cortex based on the direction of movement evoked by brief (10 ms) pulses. Prolonged trains of electrical or optogenetic stimulation (100-500 ms) targeted to anterior or posterior subregions of motor cortex evoked reproducible complex movements of the forelimb to distinct positions in space.

Simple and cost-effective hardware and software for functional brain mapping using intrinsic optical signal imaging.

We describe a simple and low-cost system for intrinsic optical signal (IOS) imaging using stable LED light sources, basic microscopes, and commonly available CCD cameras. IOS imaging measures activity-dependent changes in the light reflectance of brain tissue, and can be performed with a minimum of specialized equipment. Our system uses LED ring lights that can be mounted on standard microscope objectives or video lenses to provide a homogeneous and stable light source, with less than 0.

Automated light-based mapping of motor cortex by photoactivation of channelrhodopsin-2 transgenic mice.

Traditionally, mapping the motor cortex requires electrodes to stimulate the brain and define motor output pathways. Although effective, electrode-based methods are labor-intensive, potentially damaging to the cortex and can have off-target effects. As an alternative method of motor mapping, we photostimulated transgenic mice expressing the light-sensitive ion channel channelrhodopsin-2 in predominantly layer-5 output cortical neurons.