A neural surveyor to map touch on the body

Perhaps the most recognizable sensory map in all of neuroscience is the somatosensory homunculus. Although it seems straightforward, this simple representation belies the complex link between an activation in a somatotopic map and the associated touch location on the body. Any isolated activation is spatially ambiguous without a neural decoder that can read its position within the entire map, but how this is computed by neural networks is unknown. We propose that the somatosensory system implements multilateration, a common computation used by surveying and global positioning systems to localize objects. Specifically, to decode touch location on the body, multilateration estimates the relative distance between the afferent input and the boundaries of a body part (e.g., the joints of a limb). We show that a simple feedforward neural network, which captures several fundamental receptive field properties of cortical somatosensory neurons, can implement a Bayes-optimal multilateral computation. Simulations demonstrated that this decoder produced a pattern of localization variability between two boundaries that was unique to multilateration. Finally, we identify this computational signature of multilateration in actual psychophysical experiments, suggesting that it is a candidate computational mechanism underlying tactile localization.

Differential regulation of prelimbic and thalamic transmission to the basolateral amygdala by acetylcholine receptors

The amygdalar anterior basolateral nucleus (BLa) plays a vital role in emotional behaviors. This region receives dense cholinergic projections from basal forebrain which are critical in regulating neuronal activity and synaptic transmission. Cholinergic signaling in BLa is thought to occur through both a slow mode of volume transmission as well as a rapid, phasic mode. However, the relative effect of each mode of signaling in BLa is not understood. Here, we used electrophysiology and optogenetics in mouse brain slices to compare regulation of afferent input from cortex and thalamus to the BLa by these two modes of transmission. Phasic ACh release evoked by single pulse stimulation of cholinergic terminals had a biphasic effect on glutamatergic transmission at cortical input, producing rapid nicotinic receptor-mediated facilitation followed by slower muscarinic receptor (mAChR)-mediated depression. In contrast, tonic elevation of ACh through application of the cholinesterase inhibitor physostigmine suppressed glutamatergic transmission at cortical inputs through mAChRs only. This suppression was not observed at thalamic inputs to BLa. In agreement with this pathway-specificity, the mAChR agonist, muscarine more potently suppressed transmission at inputs from prelimbic cortex (PL) than thalamus. Muscarinic inhibition at PL input was dependent on presynaptic M4 mAChRs, while at thalamic input it depended upon M3 mAChR-mediated stimulation of retrograde endocannabinoid signaling. Muscarinic inhibition at both pathways was frequency-dependent, allowing only high frequency activity to pass. These findings demonstrate complex cholinergic regulation of afferent input to BLa that depends upon the mode of ACh release and is both pathway specific and frequency dependent.

MR-safe multisegmental vibration device for cortical mapping of paraspinal afferent input

<p>The objective of this study was to develop an MR-safe stimulation device (pneumatic vibration device, pneuVID) that can apply vibrotactile stimulation to different thoracolumbar segments and to characterize stimulation parameters such as the amplitude and its stability for two relevant frequencies (20Hz/80Hz). This is the first apparatus specifically designed for paraspinal tissue vibration on different segmental levels in an MR environment. </p>

MR-safe multisegmental vibration device for cortical mapping of paraspinal afferent input

<p>The objective of this study was to develop an MR-safe stimulation device (pneumatic vibration device, pneuVID) that can apply vibrotactile stimulation to different thoracolumbar segments and to characterize stimulation parameters such as the amplitude and its stability for two relevant frequencies (20Hz/80Hz). This is the first apparatus specifically designed for paraspinal tissue vibration on different segmental levels in an MR environment. </p>

The Effect of Limb Position on a Static Knee Extension Task can be Explained with a Simple Spinal Cord Circuit Model

The influence of proprioceptive feedback on muscle activity during isometric tasks is the subject of conflicting studies. We performed an isometric knee extension task experiment based on two common clinical tests for mobility and flexibility. The task was carried out at four pre-set angles of the knee and we recorded from five muscles for two different hip positions. We applied muscle synergy analysis using non-negative matrix factorisation on surface electromyograph recordings to identify patterns in the data which changed with internal knee angle, suggesting a link between proprioception and muscle activity. We hypothesised that such patterns arise from the way proprioceptive and cortical signals are integrated in neural circuits of the spinal cord. Using the MIIND neural simulation platform, we developed a computational model based on current understanding of spinal circuits with an adjustable afferent input. The model produces the same synergy trends as observed in the data, driven by changes in the afferent input. In order to match the activation patterns from each knee angle and position of the experiment, the model predicts the need for three distinct inputs: two to control a non-linear bias towards the extensors and against the flexors, and a further input to control additional inhibition of rectus femoris. The results show that proprioception may be involved in modulating muscle synergies encoded in cortical or spinal neural circuits.

Six-Month Lower-Leg Sensory Stimulation Augments Neural Network Connectivity Associated With Improved Gait

Foot sole somatosensory impairment associated with peripheral neuropathy (PN) is prevalent and a strong independent risk factor for gait disturbance and falls in older adults. A lower-limb sensory prosthesis providing afferent input related to foot sole pressure distributions via lower-leg vibrotactile stimulation has been demonstrated to improve gait in people with PN. The effects of this device on brain function related to motor control, however, remains equivocal. This study aimed to explore changes in brain network connectivity after six months of daily use of the prosthesis among individuals with diagnosed PN and balance problems. Functional Gait Assessment (FGA) and resting-state functional magnetic resonance imaging were completed before and after the intervention. Preliminary analysis on participants who have completed the study to date (N=5; mean age 76 years) indicated altered connectivity of the sensorimotor network (SMN), frontoparietal network (FPN), and the default mode network (DMN) post-intervention (Z&gt;3.11, unadjusted p&lt;0.05). Participants displayed an average improvement of 5.5 point in the FGA (Minimal Clinically Important Differences&gt;4 for community-dwelling older adults) that was correlated with connectivity changes (unadjusted p&lt;0.05). Specifically, improved FGA was associated with: 1) increased connectivity between the SMN, cerebellum, and occipital cortex; 2) increased connectivity between the FPN, cerebellum, calcarine and intracalcarine; and 3) decreased connectivity between DMN and intracalcarine. These early findings suggest that long-term use of a lower-limb sensory prosthesis may induce neuroplastic changes in brain network connectivity reflecting enhanced bottom-up sensory-attentional processing and suppression of the DMN that are relevant to gait improvements among older adults with PN.

Distinct dendritic Ca2+ spike forms produce opposing input-output transformations in rat CA3 pyramidal cells

Proper integration of different inputs targeting the dendritic tree of CA3 pyramidal cells (CA3PCs) is critical for associative learning and recall. Dendritic Ca2+ spikes have been proposed to perform associative computations in other PC types by detecting conjunctive activation of different afferent input pathways, initiating afterdepolarization (ADP), and triggering burst firing. Implementation of such operations fundamentally depends on the actual biophysical properties of dendritic Ca2+ spikes; yet little is known about these properties in dendrites of CA3PCs. Using dendritic patch-clamp recordings and two-photon Ca2+ imaging in acute slices from male rats, we report that, unlike CA1PCs, distal apical trunk dendrites of CA3PCs exhibit distinct forms of dendritic Ca2+ spikes. Besides ADP-type global Ca2+ spikes, a majority of dendrites expresses a novel, fast Ca2+ spike type that is initiated locally without bAPs, can recruit additional Na+ currents, and is compartmentalized to the activated dendritic subtree. Occurrence of the different Ca2+ spike types correlates with dendritic structure, indicating morpho-functional heterogeneity among CA3PCs. Importantly, ADPs and dendritically initiated spikes produce opposing somatic output: bursts versus strictly single-action potentials, respectively. The uncovered variability of dendritic Ca2+ spikes may underlie heterogeneous input-output transformation and bursting properties of CA3PCs, and might specifically contribute to key associative and non-associative computations performed by the CA3 network.

Experience-dependent plasticity in early stations of sensory processing in mature brains: effects of environmental enrichment on dendrite measures in trigeminal nuclei

Nervous systems respond with structural changes to environmental changes even in adulthood. In recent years, experience-dependent structural plasticity was shown not to be restricted to the cerebral cortex, as it also occurs at subcortical and even peripheral levels. We have previously shown that two populations of trigeminal nuclei neurons, trigeminothalamic barrelette neurons of the principal nucleus (Pr5), and intersubnuclear neurons in the caudal division of the spinal trigeminal nucleus (Sp5C) that project to Pr5 underwent morphometric and topological changes in their dendritic trees after a prolonged total or partial loss of afferent input from the vibrissae. Here we examined whether and what structural alterations could be elicited in the dendritic trees of the same cell populations in young adult rats after being exposed for 2 months to an enriched environment (EE), and how these changes evolved when animals were returned to standard housing for an additional 2 months. Neurons were retrogradely labeled with BDA delivered to, respectively, the ventral posteromedial thalamic nucleus or Pr5. Fully labeled cells were digitally reconstructed with Neurolucida and analyzed with NeuroExplorer. EE gave rise to increases in dendritic length, number of trees and branching nodes, spatial expansion of the trees, and dendritic spines, which were less pronounced in Sp5C than in Pr5 and differed between sides. In Pr5, these parameters returned, but only partially, to control values after EE withdrawal. These results underscore a ubiquity of experience-dependent changes that should not be overlooked when interpreting neuroplasticity and developing plasticity-based therapeutic strategies.

A computational model of direction selectivity in Macaque V1 cortex based on dynamic differences between ON and OFF pathways

This paper is about neural mechanisms of direction selectivity (DS) in Macaque primary visual cortex, V1. DS arises in V1 layer 4Ca, which receives afferent input from the Magnocellular division of the Lateral Geniculate Nucleus (LGN). LGN itself, however, is not direction-selective. To understand the mechanisms of DS, we built a new computational model (DSV1) of 4Ca. DSV1 is a realistic, large-scale mechanistic model that simulates many V1 properties: orientation selectivity, spatial and temporal tuning, contrast response, and DS. In the model, DS is initiated by the dynamic difference of OFF and ON Magnocellular cell activity that excites the model's layer 4Ca; the recurrent network has no intra-cortical direction-specific connections. In experiments, and in DSV1, most 4Ca Simple cells were highly direction-selective but few 4Ca Complex cells had high DS. Furthermore, the preferred directions of the model's direction- selective Simple cells were invariant with spatial and temporal frequency, in this way emulating the experimental data. The distribution of DS across the model's population of cells was very close to that found in experiments. Analyzing DSV1, we found that the dynamic interaction of feedforward and intra-cortical synaptic currents led to cortical enhancement of DS for a majority of cells. In view of the strong quantitative agreement between DS in data and in model simulations, the neural mechanisms of DS in DSV1 may be indicative of those in the real visual cortex.

Distinct dendritic Ca2+ spike forms produce opposing input-output transformations in rat CA3 pyramidal cells

Proper integration of different inputs targeting the dendritic tree of CA3 pyramidal cells (CA3PCs) is critical for associative learning and recall. Dendritic Ca2+ spikes have been proposed to perform associative computations in other PC types, by detecting conjunctive activation of different afferent input pathways, initiating afterdepolarization (ADP) and triggering burst firing. Implementation of such operations fundamentally depends on the actual biophysical properties of dendritic Ca2+ spikes; yet little is known about these properties in dendrites of CA3PCs. Using dendritic patch-clamp recordings and two-photon Ca2+ imaging in acute slices from male rats we report that, unlike CA1PCs, distal apical trunk dendrites of CA3PCs exhibit distinct forms of dendritic Ca2+ spikes. Besides ADP-type global Ca2+ spikes, a majority of dendrites expresses a novel, fast Ca2+ spike type that is initiated locally without backpropagating action potentials, can recruit additional Na+ currents, and is compartmentalized to the activated dendritic subtree. Occurrence of the different Ca2+ spike types correlates with dendritic structure, indicating morpho-functional heterogeneity among CA3PCs. Importantly, ADPs and dendritically initiated spikes produce opposing somatic output: bursts versus strictly single action potentials, respectively. The uncovered variability of dendritic Ca2+ spikes may underlie heterogeneous input-output transformation and bursting properties of CA3PCs, and might specifically contribute to key associative and non-associative computations performed by the CA3 network.