scholarly journals Differential effects of amplitude-modulated transcranial focused ultrasound on excitatory and inhibitory neurons

2020 ◽  
Author(s):  
Duc T. Nguyen ◽  
Destiny Berisha ◽  
Elisa Konofagou ◽  
Jacek P. Dmochowski
Keyword(s):  
Firing Rate ◽  
Focused Ultrasound ◽  
Multiple Scales ◽  
Brain Activity ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Inhibitory Neurons ◽  
Specific Cell ◽  
Inhibitory Interneurons ◽  
Transcranial Focused Ultrasound

AbstractAlthough stimulation with ultrasound has been shown to modulate brain activity at multiple scales, it remains unclear whether transcranial focused ultrasound stimulation (tFUS) exerts its influence on specific cell types. Here we propose a novel form of tFUS where a continuous waveform is amplitude modulated (AM) at a slow rate (i.e., 40 Hz) targeting the temporal range of electrophysiological activity: AM-tFUS. We stimulated the rat hippocampus while recording multi-unit activity (MUA) followed by classification of spike waveforms into putative excitatory pyramidal cells and inhibitory interneurons. At low acoustic intensity, AM-tFUS selectively reduced firing rates of inhibitory interneurons. On the other hand, higher intensity AM-tFUS increased firing of putative excitatory neurons with no effect on inhibitory firing. Interestingly, firing rate was unchanged during AM-tFUS at intermediate intensity. Consistent with the observed changes in firing rate, power in the theta band (3-10 Hz) of the local field potential (LFP) decreased at low-intensity, was unchanged at intermediate intensity, and increased at higher intensity. Temperature increases at the AM-tFUS target were limited to 0.2°C. Our findings indicate that inhibitory interneurons exhibit greater sensitivity to ultrasound, and that cell-type specific neuromodulation may be achieved by calibrating the intensity of AM-tFUS.

scholarly journals Bidirectional and state-dependent modulation of brain activity by transcranial focused ultrasound in non-human primates

2021 ◽  
Vol 14 (2) ◽  
pp. 261-272
Author(s):  
Pai-Feng Yang ◽  
M. Anthony Phipps ◽  
Sumeeth Jonathan ◽  
Allen T. Newton ◽  
Nellie Byun ◽  
...  
Keyword(s):  
Focused Ultrasound ◽  
Brain Activity ◽  
State Dependent ◽  
Transcranial Focused Ultrasound

scholarly journals Brain activity mapping at multiple scales with silicon microprobes containing 1,024 electrodes

2015 ◽  
Vol 114 (3) ◽  
pp. 2043-2052 ◽  
Author(s):  
Justin L. Shobe ◽  
Leslie D. Claar ◽  
Sepideh Parhami ◽  
Konstantin I. Bakhurin ◽  
Sotiris C. Masmanidis
Keyword(s):  
Multiple Scales ◽  
Functional Organization ◽  
Brain Activity ◽  
Three Dimensional ◽  
Field Potential ◽  
Neural Systems ◽  
Mammalian Brain ◽  
Neural Signals ◽  
Neural Ensembles ◽  
Potential Activity

The coordinated activity of neural ensembles across multiple interconnected regions has been challenging to study in the mammalian brain with cellular resolution using conventional recording tools. For instance, neural systems regulating learned behaviors often encompass multiple distinct structures that span the brain. To address this challenge we developed a three-dimensional (3D) silicon microprobe capable of simultaneously measuring extracellular spike and local field potential activity from 1,024 electrodes. The microprobe geometry can be precisely configured during assembly to target virtually any combination of four spatially distinct neuroanatomical planes. Here we report on the operation of such a device built for high-throughput monitoring of neural signals in the orbitofrontal cortex and several nuclei in the basal ganglia. We perform analysis on systems-level dynamics and correlations during periods of conditioned behavioral responding and rest, demonstrating the technology's ability to reveal functional organization at multiple scales in parallel in the mouse brain.

scholarly journals Intrinsic Cell-type Selectivity and Inter-neuronal Connectivity Alteration by Transcranial Focused Ultrasound

2019 ◽  
Author(s):  
Kai Yu ◽  
Xiaodan Niu ◽  
Esther Krook-Magnuson ◽  
Bin He
Keyword(s):  
Focused Ultrasound ◽  
Inhibitory Neurons ◽  
Synaptic Connectivity ◽  
Fast Spiking ◽  
First Time ◽  
Transcranial Focused Ultrasound ◽  
Specific Neuron ◽  
Ultrasound Pulse

ABSTRACTTranscranial focused ultrasound (tFUS) is a promising neuromodulation technique, but its mechanisms remain unclear. We investigate the effect of tFUS stimulation on different neuron types and synaptic connectivity in in vivo anesthetized rodent brains. Single units were separated into regular-spiking and fast-spiking units based on their extracellular spike shapes, further validated in transgenic optogenetic mice models of light-excitable excitatory and inhibitory neurons. For the first time, we show that excitatory neurons are significantly less responsive to low ultrasound pulse repetition frequencies (UPRFs), whereas the spike rates of inhibitory neurons do not change significantly across all UPRF levels. Our results suggest that we can preferentially target specific neuron types noninvasively by altering the tFUS UPRF. We also report in vivo observation of long-term synaptic connectivity changes induced by noninvasive tFUS in rats. This finding suggests tFUS can be used to encode temporally dependent stimulation paradigms into neural circuits and non-invasively elicit long-term changes in synaptic connectivity.

scholarly journals Grid cells show field-to-field variability and this explains the aperiodic response of inhibitory interneurons

2017 ◽  
Author(s):  
Benjamin Dunn ◽  
Daniel Wennberg ◽  
Ziwei Huang ◽  
Yasser Roudi
Keyword(s):  
Experimental Data ◽  
Firing Rate ◽  
Grid Cell ◽  
Network Models ◽  
Theoretical Models ◽  
Inhibitory Neurons ◽  
Inhibitory Interneurons ◽  
Grid Cells ◽  
External Stimuli ◽  
Individual Grid

AbstractResearch on network mechanisms and coding properties of grid cells assume that the firing rate of a grid cell in each of its fields is the same. Furthermore, proposed network models predict spatial regularities in the firing of inhibitory interneurons that are inconsistent with experimental data. In this paper, by analyzing the response of grid cells recorded from rats during free navigation, we first show that there are strong variations in the mean firing rate of the fields of individual grid cells and thus show that the data is inconsistent with the theoretical models that predict similar peak magnitudes. We then build a two population excitatory-inhibitory network model in which sparse spatially selective input to the excitatory cells, presumed to arise from e.g. salient external stimuli, hippocampus or a combination of both, leads to the variability in the firing field amplitudes of grid cells. We show that, when combined with appropriate connectivity between the excitatory and inhibitory neurons, the variability in the firing field amplitudes of grid cells results in inhibitory neurons that do not exhibit regular spatial firing, consistent with experimental data. Finally, we show that even if the spatial positions of the fields are maintained, variations in the firing rates of the fields of grid cells are enough to cause remapping of hippocampal cells.

scholarly journals Cell type- and activity-dependent extracellular correlates of intracellular spiking

2015 ◽  
Vol 114 (1) ◽  
pp. 608-623 ◽  
Author(s):  
Costas A. Anastassiou ◽  
Rodrigo Perin ◽  
György Buzsáki ◽  
Henry Markram ◽  
Christof Koch
Keyword(s):  
Brain Activity ◽  
Field Potential ◽  
Synaptic Activity ◽  
Inhibitory Neurons ◽  
Temporal Features ◽  
Temporal Derivative ◽  
The Common ◽  
Rat Somatosensory Cortex ◽  
Activity Dependent ◽  
Local Field Potential Lfp

Despite decades of extracellular action potential (EAP) recordings monitoring brain activity, the biophysical origin and inherent variability of these signals remain enigmatic. We performed whole cell patch recordings of excitatory and inhibitory neurons in rat somatosensory cortex slice while positioning a silicon probe in their vicinity to concurrently record intra- and extracellular voltages for spike frequencies under 20 Hz. We characterize biophysical events and properties (intracellular spiking, extracellular resistivity, temporal jitter, etc.) related to EAP recordings at the single-neuron level in a layer-specific manner. Notably, EAP amplitude was found to decay as the inverse of distance between the soma and the recording electrode with similar (but not identical) resistivity across layers. Furthermore, we assessed a number of EAP features and their variability with spike activity: amplitude (but not temporal) features varied substantially (∼30–50% compared with mean) and nonmonotonically as a function of spike frequency and spike order. Such EAP variation only partly reflects intracellular somatic spike variability and points to the plethora of processes contributing to the EAP. Also, we show that the shape of the EAP waveform is qualitatively similar to the negative of the temporal derivative to the intracellular somatic voltage, as expected from theory. Finally, we tested to what extent EAPs can impact the lowpass-filtered part of extracellular recordings, the local field potential (LFP), typically associated with synaptic activity. We found that spiking of excitatory neurons can significantly impact the LFP at frequencies as low as 20 Hz. Our results question the common assertion that the LFP acts as proxy for synaptic activity.

scholarly journals Optogenetic inhibition-mediated activity-dependent modification of CA1 pyramidal-interneuron connections during behavior

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Igor Gridchyn ◽  
Philipp Schoenenberger ◽  
Joseph O'Neill ◽  
Jozsef Csicsvari
Keyword(s):  
Firing Rate ◽  
Pyramidal Cell ◽  
Pyramidal Cells ◽  
Inhibitory Interneurons ◽  
Spike Synchrony ◽  
Synaptic Inputs ◽  
Cross Correlations ◽  
Dependent Modification ◽  
Activity Dependent

In vitro work revealed that excitatory synaptic inputs to hippocampal inhibitory interneurons could undergo Hebbian, associative, or non-associative plasticity. Both behavioral and learning-dependent reorganization of these connections has also been demonstrated by measuring spike transmission probabilities in pyramidal cell-interneuron spike cross-correlations that indicate monosynaptic connections. Here we investigated the activity-dependent modification of these connections during exploratory behavior in rats by optogenetically inhibiting pyramidal cell and interneuron subpopulations. Light application and associated firing alteration of pyramidal and interneuron populations led to lasting changes in pyramidal-interneuron connection weights as indicated by spike transmission changes. Spike transmission alterations were predicted by the light-mediated changes in the number of pre- and postsynaptic spike pairing events and by firing rate changes of interneurons but not pyramidal cells. This work demonstrates the presence of activity-dependent associative and non-associative reorganization of pyramidal-interneuron connections triggered by the optogenetic modification of the firing rate and spike synchrony of cells.

scholarly journals Transcranial Focused Ultrasound Neuromodulation: A Review of the Excitatory and Inhibitory Effects on Brain Activity in Human and Animals

2021 ◽  
Vol 15 ◽  
Author(s):  
Tingting Zhang ◽  
Na Pan ◽  
Yuping Wang ◽  
Chunyan Liu ◽  
Shimin Hu
Keyword(s):  
Focused Ultrasound ◽  
Brain Activity ◽  
Pressure Effects ◽  
Spinal Reflexes ◽  
Brain Diseases ◽  
Inhibitory Effects ◽  
Mechanical Pressure ◽  
Non Invasive ◽  
Non Destructive ◽  
Transcranial Focused Ultrasound

Non-invasive neuromodulation technology is important for the treatment of brain diseases. The effects of focused ultrasound on neuronal activity have been investigated since the 1920s. Low intensity transcranial focused ultrasound (tFUS) can exert non-destructive mechanical pressure effects on cellular membranes and ion channels and has been shown to modulate the activity of peripheral nerves, spinal reflexes, the cortex, and even deep brain nuclei, such as the thalamus. It has obvious advantages in terms of security and spatial selectivity. This technology is considered to have broad application prospects in the treatment of neurodegenerative disorders and neuropsychiatric disorders. This review synthesizes animal and human research outcomes and offers an integrated description of the excitatory and inhibitory effects of tFUS in varying experimental and disease conditions.

Dynamics of the CA3 pyramidial neuron autoassociative memory network in the hippocampus

1994 ◽  
Vol 343 (1304) ◽  
pp. 167-187 ◽  
Keyword(s):  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Recurrent Network ◽  
Inhibitory Neurons ◽  
Regulatory Function ◽  
Inhibitory Interneurons ◽  
Spatial Correlations ◽  
Temporal Correlations ◽  
Recurrent Collateral ◽  
Ca3 Region

A theory for the dynamics of sparse associative memory has been applied to the CA3 pyramidal recurrent network in the hippocampus. The CA3 region is modelled as a network of pyramidal neurons randomly connected through their recurrent collaterals. Both the elliptical spread of the axonal systems and the exponential decrease in connectivity with distance are taken into account in estimating the connection probabilities. Pyramidal neurons also receive connections from inhibitory interneurons which occur in large numbers throughout the network; these in turn receive inputs from other inhibitory interneurons and from pyramidal neurons. These inhibitory neurons are modelled as rapidly acting linear devices which produce outputs proportional to their inputs; they perform an important regulatory function in the setting of the membrane potentials of the pyramidal neurons. The probability of a neuron firing in a stored memory, which determines the average number of neurons active when a memory is recalled, can be set at will. Memories are stored at the recurrent collateral synapses using a two-valued Hebbian. Allowance is made in the theory both for the spatial correlations between the learned strengths of the recurrent collateral synapses and temporal correlations between the state of the network and these synaptic strengths. The recall of a memory begins with the firing of a set of CA3 pyramidal neurons that overlap with the memory to be recalled as well as the firing of a set of pyramidal neurons not in the memory to be recalled; the firing of both sets of neurons is probably induced by synapses formed on CA3 neurons by perforant pathway axons. The firing of different sets of pyram idal neurons then evolves by discrete synchronous steps. The CA3 recurrent network is shown to retrieve memories under specific conditions of the setting of the membrane potential of the pyramidal neurons by inhibitory interneurons. The adjustable parameters in the theory have been assigned values in accord with the known physiology of the CA3 region. Certain levels of overlap between the input and the memory to be retrieved must also be satisfied for almost complete retrieval. The number of memories which can be stored and retrieved without degradation is primarily a function of the number of active neurons when a memory is recalled and the degree of connectivity in the network. The inhomogeneity in the connectivity of the pyramidal cells improves both capacity and overlap of the final state with the memory. T he probabilistic secretion of quanta at the recurrent collateral synapses improves the recall mechanism when there is only partial overlap in the input with the memory to be retrieved and the input contains incorrect elements, at the expense of a slight deterioration in the fidelity of recall.

scholarly journals Selective, State-Dependent Activation of Somatostatin-Expressing Inhibitory Interneurons in Mouse Neocortex

2008 ◽  
Vol 100 (5) ◽  
pp. 2640-2652 ◽  
Author(s):  
Erika E. Fanselow ◽  
Kristen A. Richardson ◽  
Barry W. Connors
Keyword(s):  
Metabotropic Glutamate Receptor ◽  
Fluorescent Protein ◽  
Inhibitory Neuron ◽  
Pyramidal Cells ◽  
Inhibitory Neurons ◽  
Inhibitory Influence ◽  
Dense Layer ◽  
Inhibitory Interneurons ◽  
Receptor Agonists ◽  
Group I

The specific functions of subtypes of cortical inhibitory neurons are not well understood. This is due in part to a dearth of information about the behaviors of interneurons under conditions when the surrounding circuit is in an active state. We investigated the firing behavior of a subset of inhibitory interneurons, identified using mice that express green fluorescent protein (GFP) in a subset of somatostatin-expressing inhibitory cells (“GFP-expressing inhibitory neuron” [GIN] cells). The somata of the GIN cells were in layer 2/3 of somatosensory cortex and had dense, layer 1–projecting axons that are characteristic of Martinotti neurons. Interestingly, GIN cells fired similarly during a variety of diverse activating conditions: when bathed in fluids with low-divalent cation concentrations, when stimulated with brief trains of local synaptic inputs, when exposed to group I metabotropic glutamate receptor agonists, or when exposed to muscarinic cholinergic receptor agonists. During these manipulations, GIN cells fired rhythmically and persistently in the theta-frequency range (3–10 Hz). Synchronous firing was often observed and its strength was directly proportional to the magnitude of electrical coupling between GIN cells. These effects were cell type specific: the four manipulations that persistently activated GIN cells rarely caused spiking of regular-spiking (RS) pyramidal cells or fast-spiking (FS) inhibitory interneurons. Our results suggest that supragranular GIN interneurons form an electrically coupled network that exerts a coherent 3- to 10-Hz inhibitory influence on its targets. Because GIN cells are more readily activated than RS and FS cells, it is possible that they act as “first responders” when cortical excitatory activity increases.

scholarly journals NFTsim: Theory and Simulation of Multiscale Neural Field Dynamics

2017 ◽  
Author(s):  
P. Sanz-Leon ◽  
P. A. Robinson ◽  
S. A. Knock ◽  
P. M. Drysdale ◽  
R. G. Abeysuriya ◽  
...  
Keyword(s):  
Large Scale ◽  
Multiple Scales ◽  
Brain Activity ◽  
Field Potential ◽  
Neural Field ◽  
Neural Systems ◽  
Unified Framework ◽  
Plain Text ◽  
Wide Range ◽  
Key Aspects

AbstractA user ready, portable, documented software package, NFTsim, is presented to facilitate numerical simulations of a wide range of brain systems using continuum neural field modeling. NFTsim enables users to simulate key aspects of brain activity at multiple scales. At the microscopic scale, it incorporates characteristics of local interactions between cells, neurotransmitter effects, synaptodendritic delays and feedbacks. At the mesoscopic scale, it incorporates information about medium to large scale axonal ranges of fibers, which are essential to model dissipative wave transmission and to produce synchronous oscillations and associated cross-correlation patterns as observed in local field potential recordings of active tissue. At the scale of the whole brain, NFTsim allows for the inclusion of long range pathways, such as thalamocortical projections, when generating macroscopic activity fields. The multiscale nature of the neural activity produced by NFTsim has the potential to enable the modeling of resulting quantities measurable via various neuroimaging techniques. In this work, we give a comprehensive description of the design and implementation of the software. Due to its modularity and flexibility, NFTsim enables the systematic study of an unlimited number of neural systems with multiple neural populations under a unified framework and allows for direct comparison with analytic and experimental predictions. The code is written in C++ and bundled with Matlab routines for a rapid quantitative analysis and visualization of the outputs. The output of NFTsim is stored in plain text file enabling users to select from a broad range of tools for offline analysis. This software enables a wide and convenient use of powerful physiologically-based neural field approaches to brain modeling. NFTsim is distributed under the Apache 2.0 license.

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