Auditory Thalamocortical Transmission Is Reliable and Temporally Precise

2005 ◽  
Vol 94 (3) ◽  
pp. 2019-2030 ◽  
Author(s):  
Heather J. Rose ◽  
Raju Metherate
Keyword(s):  
Primary Auditory Cortex ◽  
Inhibitory Neurons ◽  
Latency Variability ◽  
Medial Geniculate ◽  
Low Jitter ◽  
Fast Spiking ◽  
Whole Cell Recordings ◽  
Minimal Stimulation ◽  
Juvenile Mouse

We have used the auditory thalamocortical slice to characterize thalamocortical transmission in primary auditory cortex (ACx) of the juvenile mouse. “Minimal” stimulation was used to activate medial geniculate neurons during whole cell recordings from regular-spiking (RS cells; mostly pyramidal) and fast-spiking (FS, putative inhibitory) neurons in ACx layers 3 and 4. Excitatory postsynaptic potentials (EPSPs) were considered monosynaptic (thalamocortical) if they met three criteria: low onset latency variability (jitter), little change in latency with increased stimulus intensity, and little change in latency during a high-frequency tetanus. Thalamocortical EPSPs were reliable (probability of postsynaptic responses to stimulation was ∼1.0) as well as temporally precise (low jitter). Both RS and FS neurons received thalamocortical input, but EPSPs in FS cells had faster rise times, shorter latencies to peak amplitude, and shorter durations than EPSPs in RS cells. Thalamocortical EPSPs depressed during repetitive stimulation at rates (2–300 Hz) consistent with thalamic spike rates in vivo, but at stimulation rates ≥40 Hz, EPSPs also summed to activate N-methyl-d-aspartate receptors and trigger long-lasting polysynaptic activity. We conclude that thalamic inputs to excitatory and inhibitory neurons in ACx activate reliable and temporally precise monosynaptic EPSPs that in vivo may contribute to the precise timing of acoustic-evoked responses.

scholarly journals Estrus-Cycle Regulation of Cortical Inhibition

2018 ◽  
Author(s):  
Ann M. Clemens ◽  
Constanze Lenschow ◽  
Prateep Beed ◽  
Lanxiang Li ◽  
Rosanna Sammons ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Β ◽  
Cortical Inhibition ◽  
Female Rats ◽  
Estrus Cycle ◽  
Whole Cell ◽  
Fast Spiking ◽  
Whole Cell Recordings

SummaryFemale mammals experience cyclical changes in sexual receptivity known as the estrus-cycle. Little is known about how estrus affects the cortex although alterations in sensation, cognition and the cyclic occurrence of epilepsy suggest brain-wide processing changes. We performedin vivojuxtacellular and whole-cell recordings in somatosensory cortex of female rats and found that the estrus-cycle potently altered cortical inhibition. Fast-spiking interneurons strongly varied their activity with the estrus-cycle and estradiol in ovariectomized females, while regular-spiking excitatory neurons did not change.In vivowhole-cell recordings revealed a varying excitation-to-inhibition-ratio with estrus.In situhybridization for estrogen receptor β (Esr2) showed co-localization with parvalbumin-positive interneurons in deep cortical layers, mirroring the laminar distribution of our physiological findings.In vivoandin vitroexperiments confirmed that estrogen acts locally to increase fast-spiking interneuron excitability through an estrogen receptor β mechanism. We conclude that sex hormones powerfully modulate cortical inhibition in the female 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 Characterization of thalamocortical responses of regular-spiking and fast-spiking neurons of the mouse auditory cortex in vitro and in silico

2012 ◽  
Vol 107 (5) ◽  
pp. 1476-1488 ◽  
Author(s):  
Max L. Schiff ◽  
Alex D. Reyes
Keyword(s):  
Auditory Cortex ◽  
Pyramidal Neurons ◽  
Modulation Frequency ◽  
Primary Auditory Cortex ◽  
Cortical Inhibition ◽  
Membrane Properties ◽  
Thalamic Stimulation ◽  
Fast Spiking

We use a combination of in vitro whole cell recordings and computer simulations to characterize the cellular and synaptic properties that contribute to processing of auditory stimuli. Using a mouse thalamocortical slice preparation, we record the intrinsic membrane properties and synaptic properties of layer 3/4 regular-spiking (RS) pyramidal neurons and fast-spiking (FS) interneurons in primary auditory cortex (AI). We find that postsynaptic potentials (PSPs) evoked in FS cells are significantly larger and depress more than those evoked in RS cells after thalamic stimulation. We use these data to construct a simple computational model of the auditory thalamocortical circuit and find that the differences between FS and RS cells observed in vitro generate model behavior similar to that observed in vivo. We examine how feedforward inhibition and synaptic depression affect cortical responses to time-varying inputs that mimic sinusoidal amplitude-modulated tones. In the model, the balance of cortical inhibition and thalamic excitation evolves in a manner that depends on modulation frequency (MF) of the stimulus and determines cortical response tuning.

scholarly journals Microcircuits of excitatory and inhibitory neurons in layer 2/3 of mouse barrel cortex

2012 ◽  
Vol 107 (11) ◽  
pp. 3116-3134 ◽  
Author(s):  
Michael Avermann ◽  
Christian Tomm ◽  
Celine Mateo ◽  
Wulfram Gerstner ◽  
Carl C. H. Petersen
Keyword(s):  
Barrel Cortex ◽  
Gabaergic Neurons ◽  
Network Activity ◽  
Inhibitory Neurons ◽  
Synaptic Connectivity ◽  
Postsynaptic Potentials ◽  
Optogenetic Stimulation ◽  
Layer 2 ◽  
Fast Spiking ◽  
Whole Cell Recordings

Synaptic interactions between nearby excitatory and inhibitory neurons in the neocortex are thought to play fundamental roles in sensory processing. Here, we have combined optogenetic stimulation, whole cell recordings, and computational modeling to define key functional microcircuits within layer 2/3 of mouse primary somatosensory barrel cortex. In vitro optogenetic stimulation of excitatory layer 2/3 neurons expressing channelrhodopsin-2 evoked a rapid sequence of excitation followed by inhibition. Fast-spiking (FS) GABAergic neurons received large-amplitude, fast-rising depolarizing postsynaptic potentials, often driving action potentials. In contrast, the same optogenetic stimulus evoked small-amplitude, subthreshold postsynaptic potentials in excitatory and non-fast-spiking (NFS) GABAergic neurons. To understand the synaptic mechanisms underlying this network activity, we investigated unitary synaptic connectivity through multiple simultaneous whole cell recordings. FS GABAergic neurons received unitary excitatory postsynaptic potentials with higher probability, larger amplitudes, and faster kinetics compared with NFS GABAergic neurons and other excitatory neurons. Both FS and NFS GABAergic neurons evoked robust inhibition on postsynaptic layer 2/3 neurons. A simple computational model based on the experimentally determined electrophysiological properties of the different classes of layer 2/3 neurons and their unitary synaptic connectivity accounted for key aspects of the network activity evoked by optogenetic stimulation, including the strong recruitment of FS GABAergic neurons acting to suppress firing of excitatory neurons. We conclude that FS GABAergic neurons play an important role in neocortical microcircuit function through their strong local synaptic connectivity, which might contribute to driving sparse coding in excitatory layer 2/3 neurons of mouse barrel cortex in vivo.

scholarly journals Interhemispheric callosal projections enforce response fidelity and frequency tuning in auditory cortex

2020 ◽  
Author(s):  
Bernard J. Slater ◽  
Jeffry S. Isaacson
Keyword(s):  
Auditory Cortex ◽  
Frequency Tuning ◽  
Cell Activity ◽  
Primary Auditory Cortex ◽  
Pyramidal Cells ◽  
Brain Hemispheres ◽  
Fast Spiking ◽  
Evoked Activity ◽  
Link Information

AbstractSensory cortical areas receive glutamatergic callosal projections that link information processing between brain hemispheres. However, the role of interhemispheric projections in sensory processing is unclear. Here we use single unit recordings and optogenetic manipulations in awake mice to probe how callosal inputs modulate spontaneous and tone-evoked activity in primary auditory cortex (A1). Although activation of callosal fibers increased firing of some pyramidal cells, the majority of responsive cells were suppressed. In contrast, callosal stimulation consistently increased fast spiking (FS) cell activity and brain slice recordings indicated that parvalbumin (PV)-expressing cells receive stronger callosal input than pyramidal cells or other interneuron subtypes. In vivo silencing of the contralateral cortex revealed that callosal inputs linearly modulate tone-evoked pyramidal cell activity via both multiplicative and subtractive operations. These results suggest that callosal input regulates both the salience and tuning sharpness of tone responses in A1 via PV cell-mediated feedforward inhibition.

scholarly journals Long-Term Enhancement of NMDA Receptor Function in Inhibitory Neurons Preferentially Modulates Potassium Channels and Cell Adhesion Molecules

2022 ◽  
Vol 12 ◽  
Author(s):  
Dan Xia ◽  
Xinyang Zhang ◽  
Di Deng ◽  
Xiaoyan Ma ◽  
Samer Masri ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Primary Auditory Cortex ◽  
Inhibitory Neurons ◽  
Brain Diseases ◽  
The Impact

Effectively enhancing the activity of inhibitory neurons has great therapeutic potentials since their reduced function/activity has significant contributions to pathology in various brain diseases. We showed previously that NMDAR positive allosteric modulator GNE-8324 and M-8324 selectively increase NMDAR activity on the inhibitory neurons and elevates their activity in vitro and in vivo. Here we examined the impact of long-term administering M-8324 on the functions and transcriptional profiling of parvalbumin-containing neurons in two representative brain regions, primary auditory cortex (Au1) and prelimbic prefrontal cortex (PrL-PFC). We found small changes in key electrophysiological parameters and RNA levels of neurotransmitter receptors, Na+ and Ca2+ channels. In contrast, large differences in cell adhesion molecules and K+ channels were found between Au1 and PrL-PFC in drug-naïve mice, and differences in cell adhesion molecules became much smaller after M-8324 treatment. There was also minor impact of M-8324 on cell cycle and apoptosis, suggesting a fine safety profile.

scholarly journals A Critical Role of Inhibition in Temporal Processing Maturation in the Primary Auditory Cortex

2017 ◽  
Vol 28 (5) ◽  
pp. 1610-1624 ◽  
Author(s):  
Dongqin Cai ◽  
Rongrong Han ◽  
Miaomiao Liu ◽  
Fenghua Xie ◽  
Ling You ◽  
...  
Keyword(s):  
Auditory Cortex ◽  
Temporal Processing ◽  
Critical Role ◽  
Primary Auditory Cortex ◽  
Cortical Inhibition ◽  
Fast Spiking ◽  
Processing Mechanisms

Abstract Faithful representation of sound envelopes in primary auditory cortex (A1) is vital for temporal processing and perception of natural sounds. However, the emergence of cortical temporal processing mechanisms during development remains poorly understood. Although cortical inhibition has been proposed to play an important role in this process, direct in-vivo evidence has been lacking. Using loose-patch recordings in rat A1 immediately after hearing onset, we found that stimulus-following ability in fast-spiking neurons was significantly better than in regular-spiking (RS) neurons. In-vivo whole-cell recordings of RS neurons revealed that inhibition in the developing A1 demonstrated much weaker adaptation to repetitive stimuli than in adult A1. Furthermore, inhibitory synaptic inputs were of longer duration than observed in vitro and in adults. Early in development, overlap of the prolonged inhibition evoked by 2 closely following stimuli disrupted the classical temporal sequence between excitation and inhibition, resulting in slower following capacity. During maturation, inhibitory duration gradually shortened accompanied by an improving temporal following ability of RS neurons. Both inhibitory duration and stimulus-following ability demonstrated exposure-based plasticity. These results demonstrate the role of inhibition in setting the pace for experience-dependent maturation of temporal processing in the auditory cortex.

scholarly journals Two modes of inhibitory neuronal shutdown distinctly amplify seizures in humans

2020 ◽  
Author(s):  
Omar J. Ahmed ◽  
Tibin T. John ◽  
Shyam K. Sudhakar ◽  
Ellen K.W. Brennan ◽  
Alcides Lorenzo Gonzalez ◽  
...  
Keyword(s):  
Brain Function ◽  
Action Potentials ◽  
Computational Models ◽  
Neuronal Firing ◽  
Inhibitory Neurons ◽  
Normal Brain ◽  
Neuronal Control ◽  
Normal Brain Function ◽  
Fast Spiking

ABSTRACTInhibitory neurons are critical for normal brain function but dysregulated in disorders such as epilepsy. At least two theories exist for how inhibition may acutely decrease during a seizure: hyperpolarization of fast-spiking (FS) inhibitory neurons by other inhibitory neurons, or depolarization block (DB) of FS neurons resulting in an inability to fire action potentials. Firing rate alone is unable to disambiguate these alternatives. Here, we show that human FS neurons can stop firing due to both hyperpolarization and DB within the same seizure. However, only DB of FS cells is associated with dramatic increases in local seizure amplitude, unobstructed traveling waves, and transient increases in excitatory neuronal firing. This result is independent of seizure etiology or focus. Computational models of DB reproduce the in vivo human biophysics. These methods enable intracellular decoding using only extracellular recordings in humans and explain the otherwise ambiguous inhibitory neuronal control of human seizures.

scholarly journals Neuropeptide Y expression defines a novel class of GABAergic projection neuron in the inferior colliculus

2019 ◽  
Author(s):  
Marina A. Silveira ◽  
Justin D. Anair ◽  
Nichole L. Beebe ◽  
Pooyan Mirjalili ◽  
Brett R. Schofield ◽  
...  
Keyword(s):  
Neuropeptide Y ◽  
Inferior Colliculus ◽  
Projection Neuron ◽  
Central Nucleus ◽  
Inhibitory Neurons ◽  
Multifaceted Approach ◽  
Functional Roles ◽  
Reporter Mice ◽  
Medial Geniculate ◽  
Whole Cell Recordings

Located in the midbrain, the inferior colliculus (IC) integrates information from numerous auditory nuclei and is an important hub for sound processing. Despite its importance, little is known about the molecular identity and functional roles of defined neuron types in the IC. Using a multifaceted approach in mice, we found that neuropeptide Y (NPY) expression identifies a major class of inhibitory neurons, accounting for approximately one-third of GABAergic neurons in the IC. Retrograde tracing showed that NPY neurons are principal neurons that can project to the medial geniculate nucleus. In brain slice recordings, many NPY neurons fired spontaneously, suggesting that NPY neurons may drive tonic inhibition onto postsynaptic targets. Morphological reconstructions showed that NPY neurons are stellate cells, and the dendrites of NPY neurons in the tonotopically-organized central nucleus of the IC cross isofrequency laminae. Immunostaining confirmed that NPY neurons express NPY, and we therefore hypothesized that NPY signaling regulates activity in the IC. In crosses between Npy1rcre and Ai14 Cre-reporter mice, we found that NPY Y1 receptor (Y1R)-expressing neurons are glutamatergic and were broadly distributed throughout the rostro-caudal extent of the IC. In whole-cell recordings, application of a high affinity Y1R agonist led to hyperpolarization in most Y1R-expressing IC neurons. Thus, NPY neurons represent a novel class of inhibitory principal neurons that are well poised to use GABAergic and NPY signaling to regulate the excitability of circuits in the IC and auditory thalamus.

scholarly journals Intrinsic functional neuron-type selectivity of transcranial focused ultrasound neuromodulation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kai Yu ◽  
Xiaodan Niu ◽  
Esther Krook-Magnuson ◽  
Bin He
Keyword(s):  
Focused Ultrasound ◽  
Pulse Repetition Frequency ◽  
Inhibitory Neurons ◽  
Neuron Populations ◽  
Electrophysiological Recordings ◽  
Fast Spiking ◽  
Functional Neuron ◽  
Transcranial Focused Ultrasound ◽  
Ultrasound Pulse

AbstractTranscranial focused ultrasound (tFUS) is a promising neuromodulation technique, but its mechanisms remain unclear. We hypothesize that if tFUS parameters exhibit distinct modulation effects in different neuron populations, then the mechanism can be understood through identifying unique features in these neuron populations. In this work, we investigate the effect of tFUS stimulation on different functional neuron types in in vivo anesthetized rodent brains. Single neuron recordings were separated into regular-spiking and fast-spiking units based on their extracellular spike shapes acquired through intracranial electrophysiological recordings, and further validated in transgenic optogenetic mice models of light-excitable excitatory and inhibitory neurons. We show that excitatory and inhibitory neurons are intrinsically different in response to ultrasound pulse repetition frequency (PRF). The results suggest that we can preferentially target specific neuron types noninvasively by tuning the tFUS PRF. Chemically deafened rats and genetically deafened mice were further tested for validating the directly local neural effects induced by tFUS without potential auditory confounds.

Sign in / Sign up

Export Citation Format

Share Document