GraFT: Graph Filtered Temporal Dictionary Learning for Functional Neural Imaging.

Optical imaging of calcium signals in the brain has enabled researchers to observe the activity of hundreds-to-thousands of individual neurons simultaneously. Current methods predominantly use morphological information, typically focusing on expected shapes of cell bodies, to better identify neurons in the field-of-view. The explicit shape constraints limit the applicability of automated cell identification to other important imaging scales with more complex morphologies, e.

Dynamic compartmental computations in tuft dendrites of layer 5 neurons during motor behavior.

Tuft dendrites of layer 5 pyramidal neurons form specialized compartments important for motor learning and performance, yet their computational capabilities remain unclear. Structural-functional mapping of the tuft tree from the motor cortex during motor tasks revealed two morphologically distinct populations of layer 5 pyramidal tract neurons (PTNs) that exhibit specific tuft computational properties. Early bifurcating and large nexus PTNs showed marked tuft functional compartmentalization, representing different motor variable combinations within and between their two tuft hemi-trees.

Plasticity of olfactory bulb inputs mediated by dendritic NMDA-spikes in rodent piriform cortex.

The piriform cortex (PCx) is essential for learning of odor information. The current view postulates that odor learning in the PCx is mainly due to plasticity in intracortical (IC) synapses, while odor information from the olfactory bulb carried via the lateral olfactory tract (LOT) is 'hardwired.' Here, we revisit this notion by studying location- and pathway-dependent plasticity rules.

State-Dependent Synchrony and Functional Connectivity in the Primary and Secondary Whisker Somatosensory Cortices.

Synchronized activity plays an important role in sensory coding and memory and is a hallmark of functional network connectivity. However, the effect of sensory activation on synchronization and cortical functional connectivity is largely unknown. In this study, we investigated the effect of whisker activation on synchronization and functional connectivity of the primary (wS1) and secondary (wS2) whisker somatosensory cortices at the single-cell level.

Intrinsic Disruption of the M1 Cortical Network in a Mouse Model of Parkinson's Disease.

Background: Parkinson's disease (PD) disrupts motor performance by affecting the basal ganglia system. Yet, despite the critical position of the primary motor cortex in linking basal ganglia computations with motor performance, its contribution to motor disability in PD is largely unknown. The objective of this study was to characterize the role of the primary motor cortex in PD-related motor disability.

Cell-Type-Specific Outcome Representation in the Primary Motor Cortex.

Adaptive movements are critical for animal survival. To guide future actions, the brain monitors various outcomes, including achievement of movement and appetitive goals. The nature of these outcome signals and their neuronal and network realization in the motor cortex (M1), which directs skilled movements, is largely unknown.

NMDA spikes mediate amplification of inputs in the rat piriform cortex.

The piriform cortex (PCx) receives direct input from the olfactory bulb (OB) and is the brain's main station for odor recognition and memory. The transformation of the odor code from OB to PCx is profound: mitral and tufted cells in olfactory glomeruli respond to individual odorant molecules, whereas pyramidal neurons (PNs) in the PCx responds to multiple, apparently random combinations of activated glomeruli. How these 'discontinuous' receptive fields are formed from OB inputs remains unknown.

The Many Worlds of Plasticity Rules.

Two recent papers have tackled the fundamental questions of how place fields are formed in a new environment and what plasticity mechanisms contribute to this process. Bittner et al., in their recent publication, discovered a novel plasticity rule that, in contrast to previous rules, spans the behavioral, seconds-long, timescale.

Synaptic plasticity in dendrites: complications and coping strategies.

The elaborate morphology, nonlinear membrane mechanisms and spatiotemporally varying synaptic activation patterns of dendrites complicate the expression, compartmentalization and modulation of synaptic plasticity. To grapple with this complexity, we start with the observation that neurons in different brain areas face markedly different learning problems, and dendrites of different neuron types contribute to the cell's input-output function in markedly different ways. By committing to specific assumptions regarding a neuron's learning problem and its input-output function, specific inferences can be drawn regarding the synaptic plasticity mechanisms and outcomes that we 'ought' to expect for that neuron.

Feedforward motor information enhances somatosensory responses and sharpens angular tuning of rat S1 barrel cortex neurons.

The primary vibrissae motor cortex (vM1) is responsible for generating whisking movements. In parallel, vM1 also sends information directly to the sensory barrel cortex (vS1). In this study, we investigated the effects of vM1 activation on processing of vibrissae sensory information in vS1 of the rat.

A Designer AAV Variant Permits Efficient Retrograde Access to Projection Neurons.

Efficient retrograde access to projection neurons for the delivery of sensors and effectors constitutes an important and enabling capability for neural circuit dissection. Such an approach would also be useful for gene therapy, including the treatment of neurodegenerative disorders characterized by pathological spread through functionally connected and highly distributed networks. Viral vectors, in particular, are powerful gene delivery vehicles for the nervous system, but all available tools suffer from inefficient retrograde transport or limited clinical potential.

A Novel Form of Local Plasticity in Tuft Dendrites of Neocortical Somatosensory Layer 5 Pyramidal Neurons.

Tuft dendrites of layer 5 pyramidal neurons form a separate biophysical and processing compartment. Presently, little is known about plasticity mechanisms in this isolated compartment. Here, we describe a novel form of plasticity in which unpaired low-frequency (0.

The alanine-serine-cysteine-1 (Asc-1) transporter controls glycine levels in the brain and is required for glycinergic inhibitory transmission.

Asc-1 (SLC7A10) is an amino acid transporter whose deletion causes neurological abnormalities and early postnatal death in mice. Using metabolomics and behavioral and electrophysiological methods, we demonstrate that Asc-1 knockout mice display a marked decrease in glycine levels in the brain and spinal cord along with impairment of glycinergic inhibitory transmission, and a hyperekplexia-like phenotype that is rescued by replenishing brain glycine. Asc-1 works as a glycine and L-serine transporter, and its transport activity is required for the subsequent conversion of L-serine into glycine in vivo.

An Augmented Two-Layer Model Captures Nonlinear Analog Spatial Integration Effects in Pyramidal Neuron Dendrites.

In pursuit of the goal to understand and eventually reproduce the diverse functions of the brain, a key challenge lies in reverse engineering the peculiar biology-based "technology" that underlies the brain's remarkable ability to process and store information. The basic building block of the nervous system is the nerve cell, or "neuron," yet after more than 100 years of neurophysiological study and 60 years of modeling, the information processing functions of individual neurons, and the parameters that allow them to engage in so many different types of computation (sensory, motor, mnemonic, executive, etc.) remain poorly understood.

Texture coarseness responsive neurons and their mapping in layer 2-3 of the rat barrel cortex in vivo.

Texture discrimination is a fundamental function of somatosensory systems, yet the manner by which texture is coded and spatially represented in the barrel cortex are largely unknown. Using in vivo two-photon calcium imaging in the rat barrel cortex during artificial whisking against different surface coarseness or controlled passive whisker vibrations simulating different coarseness, we show that layer 2-3 neurons within barrel boundaries differentially respond to specific texture coarsenesses, while only a minority of neurons responded monotonically with increased or decreased surface coarseness. Neurons with similar preferred texture coarseness were spatially clustered.

Active properties of neocortical pyramidal neuron dendrites.

Dendrites are the main recipients of synaptic inputs and are important sites that determine neurons' input-output functions. This review focuses on thin neocortical dendrites, which receive the vast majority of synaptic inputs in cortex but also have specialized electrogenic properties. We present a simplified working-model biophysical scheme of pyramidal neurons that attempts to capture the essence of their dendritic function, including the ability to behave under plausible conditions as dynamic computational subunits.

Nonlinear dendritic processing determines angular tuning of barrel cortex neurons in vivo.

Layer 4 neurons in primary sensory cortices receive direct sensory information from the external world. A general feature of these neurons is their selectivity to specific features of the sensory stimulation. Various theories try to explain the manner in which these neurons are driven by their incoming sensory information.

Location-dependent excitatory synaptic interactions in pyramidal neuron dendrites.

Neocortical pyramidal neurons (PNs) receive thousands of excitatory synaptic contacts on their basal dendrites. Some act as classical driver inputs while others are thought to modulate PN responses based on sensory or behavioral context, but the biophysical mechanisms that mediate classical-contextual interactions in these dendrites remain poorly understood. We hypothesized that if two excitatory pathways bias their synaptic projections towards proximal vs.

Location-dependent effects of inhibition on local spiking in pyramidal neuron dendrites.

Cortical computations are critically dependent on interactions between pyramidal neurons (PNs) and a menagerie of inhibitory interneuron types. A key feature distinguishing interneuron types is the spatial distribution of their synaptic contacts onto PNs, but the location-dependent effects of inhibition are mostly unknown, especially under conditions involving active dendritic responses. We studied the effect of somatic vs.

Calcium handling in human induced pluripotent stem cell derived cardiomyocytes.

Background: The ability to establish human induced pluripotent stem cells (hiPSCs) by reprogramming of adult fibroblasts and to coax their differentiation into cardiomyocytes opens unique opportunities for cardiovascular regenerative and personalized medicine. In the current study, we investigated the Ca(2+)-handling properties of hiPSCs derived-cardiomyocytes (hiPSC-CMs).

Methodology/principal Findings: RT-PCR and immunocytochemistry experiments identified the expression of key Ca(2+)-handling proteins.

Dynamics of excitability over extended timescales in cultured cortical neurons.

Although neuronal excitability is well understood and accurately modeled over timescales of up to hundreds of milliseconds, it is currently unclear whether extrapolating from this limited duration to longer behaviorally relevant timescales is appropriate. Here we used an extracellular recording and stimulation paradigm that extends the duration of single-neuron electrophysiological experiments, exposing the dynamics of excitability in individual cultured cortical neurons over timescales hitherto inaccessible. We show that the long-term neuronal excitability dynamics is unstable and dominated by critical fluctuations, intermittency, scale-invariant rate statistics, and long memory.

Encoding and decoding bursts by NMDA spikes in basal dendrites of layer 5 pyramidal neurons.

Bursts of action potentials are important information-bearing signals in the brain, although the neuronal specializations underlying burst generation and detection are only partially understood. In apical dendrites of neocortical pyramidal neurons, calcium spikes are known to contribute to burst generation, but a comparable understanding of basal dendritic mechanisms is lacking. Here we show that NMDA spikes in basal dendrites mediate both detection and generation of bursts through a postsynaptic mechanism.