scholarly journals Temporally precise control of single-neuron spiking by juxtacellular nanostimulation

2017 ◽  
Vol 117 (3) ◽  
pp. 1363-1378 ◽  
Author(s):  
Maik C. Stüttgen ◽  
Lourens J. P. Nonkes ◽  
H. Rüdiger A. P. Geis ◽  
Paul H. Tiesinga ◽  
Arthur R. Houweling
Keyword(s):  
Short Duration ◽  
Cortical Neurons ◽  
Action Potentials ◽  
Neural Coding ◽  
Spike Trains ◽  
Precise Control ◽  
Neuronal Spike Trains ◽  
The Impact ◽  
Activity Dependent

Temporal patterns of action potentials influence a variety of activity-dependent intra- and intercellular processes and play an important role in theories of neural coding. Elucidating the mechanisms underlying these phenomena requires imposing spike trains with precisely defined patterns, but this has been challenging due to the limitations of existing stimulation techniques. Here we present a new nanostimulation method providing control over the action potential output of individual cortical neurons. Spikes are elicited through the juxtacellular application of short-duration fluctuating currents (“kurzpulses”), allowing for the sub-millisecond precise and reproducible induction of arbitrary patterns of action potentials at all physiologically relevant firing frequencies (<120 Hz), including minute-long spike trains recorded in freely moving animals. We systematically compared our method to whole cell current injection, as well as optogenetic stimulation, and show that nanostimulation performance compares favorably with these techniques. This new nanostimulation approach is easily applied, can be readily performed in awake behaving animals, and thus promises to be a powerful tool for systematic investigations into the temporal elements of neural codes, as well as the mechanisms underlying a wide variety of activity-dependent cellular processes. NEW & NOTEWORTHY Assessing the impact of temporal features of neuronal spike trains requires imposing arbitrary patterns of spiking on individual neurons during behavior, but this has been difficult to achieve due to limitations of existing stimulation methods. We present a technique that overcomes these limitations by using carefully designed short-duration fluctuating juxtacellular current injections, which allow for the precise and reliable evocation of arbitrary patterns of neuronal spikes in single neurons in vivo.

Electrophysiological Classes of Cat Primary Visual Cortical Neurons In Vivo as Revealed by Quantitative Analyses

2003 ◽  
Vol 89 (3) ◽  
pp. 1541-1566 ◽  
Author(s):  
Lionel G. Nowak ◽  
Rony Azouz ◽  
Maria V. Sanchez-Vives ◽  
Charles M. Gray ◽  
David A. McCormick
Keyword(s):  
Short Duration ◽  
Cortical Neurons ◽  
Action Potentials ◽  
Low Frequency ◽  
Pyramidal Cells ◽  
Spike Frequency ◽  
Spike Frequency Adaptation ◽  
Frequency Adaptation ◽  
Layer 4

To facilitate the characterization of cortical neuronal function, the responses of cells in cat area 17 to intracellular injection of current pulses were quantitatively analyzed. A variety of response variables were used to separate the cells into subtypes using cluster analysis. Four main classes of neurons could be clearly distinguished: regular spiking (RS), fast spiking (FS), intrinsic bursting (IB), and chattering (CH). Each of these contained significant subclasses. RS neurons were characterized by trains of action potentials that exhibited spike frequency adaptation. Morphologically, these cells were spiny stellate cells in layer 4 and pyramidal cells in layers 2, 3, 5, and 6. FS neurons had short-duration action potentials (<0.5 ms at half height), little or no spike frequency adaptation, and a steep relationship between injected current intensity and spike discharge frequency. Morphologically, these cells were sparsely spiny or aspiny nonpyramidal cells. IB neurons typically generated a low frequency (<425 Hz) burst of spikes at the beginning of a depolarizing current pulse followed by a tonic train of action potentials for the remainder of the pulse. These cells were observed in all cortical layers, but were most abundant in layer 5. Finally, CH neurons generated repetitive, high-frequency (350–700 Hz) bursts of short-duration (<0.55 ms) action potentials. Morphologically, these cells were layer 2–4 (mainly layer 3) pyramidal or spiny stellate neurons. These results indicate that firing properties do not form a continuum and that cortical neurons are members of distinct electrophysiological classes and subclasses.

scholarly journals Response Variability and Timing Precision of Neuronal Spike Trains In Vivo

1997 ◽  
Vol 77 (5) ◽  
pp. 2836-2841 ◽  
Author(s):  
Daniel S. Reich ◽  
Jonathan D. Victor ◽  
Bruce W. Knight ◽  
Tsuyoshi Ozaki ◽  
Ehud Kaplan
Keyword(s):  
Neural Coding ◽  
Ganglion Cells ◽  
Spike Trains ◽  
Response Variability ◽  
Temporal Precision ◽  
Neuronal Spike ◽  
Timing Precision ◽  
High Stimulus ◽  
Neuronal Spike Trains

Reich, Daniel S., Jonathan D. Victor, Bruce W. Knight, Tsuyoshi Ozaki, and Ehud Kaplan. Response variability and timing precision of neuronal spike trains in vivo. J. Neurophysiol. 77: 2836–2841, 1977. We report that neuronal spike trains can exhibit high, stimulus-dependent temporal precision even while the trial-to-trial response variability, measured in several traditional ways, remains substantially independent of the stimulus. We show that retinal ganglion cells and neurons in the lateral geniculate nucleus (LGN) of cats in vivo display both these aspects of firing behavior, which have previously been reported to be contradictory. We develop a simple model that treats neurons as “leaky” integrate-and-fire devices and show that it, too, can exhibit both behaviors. We consider the implications of our findings for the problem of neural coding.

scholarly journals The Impact of Spike Timing Variability on the Signal-Encoding Performance of Neural Spiking Models

2002 ◽  
Vol 14 (2) ◽  
pp. 347-367 ◽  
Author(s):  
Amit Manwani ◽  
Peter N. Steinmetz ◽  
Christof Koch
Keyword(s):  
Channel Model ◽  
Spike Trains ◽  
Spike Timing ◽  
Noise Sources ◽  
Timing Variability ◽  
Optimal Linear ◽  
Signal Encoding ◽  
Neuronal Spike Trains ◽  
The Impact

It remains unclear whether the variability of neuronal spike trains in vivo arises due to biological noise sources or represents highly precise encoding of temporally varying synaptic input signals. Determining the variability of spike timing can provide fundamental insights into the nature of strategies used in the brain to represent and transmit information in the form of discrete spike trains. In this study, we employ a signal estimation paradigm to determine how variability in spike timing affects encoding of random time-varying signals. We assess this for two types of spiking models: an integrate-and-fire model with random threshold and a more biophysically realistic stochastic ion channel model. Using the coding fraction and mutual information as information-theoretic measures, we quantify the efficacy of optimal linear decoding of random inputs from the model outputs and study the relationship between efficacy and variability in the output spike train. Our findings suggest that variability does not necessarily hinder signal decoding for the biophysically plausible encoders examined and that the functional role of spiking variability depends intimately on the nature of the encoder and the signal processing task; variability can either enhance or impede decoding performance.

scholarly journals Striatal seeding of protofibrillar alpha-synuclein causes cortical hyperreactivity in behaving mice

2020 ◽  
Author(s):  
Sonja Blumenstock ◽  
Fanfan Sun ◽  
Petar Marinković ◽  
Carmelo Sgobio ◽  
Sabine Liebscher ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Alpha Synuclein ◽  
Cellular Level ◽  
Neuronal Function ◽  
Two Photon ◽  
Neuron Function ◽  
The Impact ◽  
Self Aggregation ◽  
Intrastriatal Injection

SummaryAlpha-synucleinopathies are characterized by self-aggregation of the protein alpha-synuclein (a-syn), causing alterations on the molecular and cellular level. To unravel the impact of transneuronal spreading and templated misfolding of a-syn on the microcircuitry of remotely connected brain areas, we investigated cortical neuron function in awake mice 9 months after a single intrastriatal injection of a-syn preformed fibrils (PFFs), using in vivo two-photon calcium imaging. We found altered function of layer 2/3 cortical neurons in somatosensory cortex (S1) of PFF-inoculated mice, as witnessed by an enhanced response to whisking and increased synchrony, accompanied by a decrease in baseline Ca2+ levels. Stereological analyses revealed a reduction in GAD67-positive inhibitory cells in S1 in PFF-injected brains. These findings point to a disturbed excitation/inhibition balance as an important pathomechanism in alpha-synucleinopathies and demonstrate a clear association between the spread of toxic proteins and the initiation of altered neuronal function in remotely connected areas.

scholarly journals Ras-like Gem GTPase induced by Npas4 promotes activity-dependent neuronal tolerance for ischemic stroke

2021 ◽  
Vol 118 (32) ◽  
pp. e2018850118
Author(s):  
Hiroo Takahashi ◽  
Ryo Asahina ◽  
Masayuki Fujioka ◽  
Takeshi K. Matsui ◽  
Shigeki Kato ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cortical Neurons ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Small Gtpase ◽  
Neuroprotective Effects ◽  
Necessary And Sufficient ◽  
Activity Dependent

Ischemic stroke, which results in loss of neurological function, initiates a complex cascade of pathological events in the brain, largely driven by excitotoxic Ca2+ influx in neurons. This leads to cortical spreading depolarization, which induces expression of genes involved in both neuronal death and survival; yet, the functions of these genes remain poorly understood. Here, we profiled gene expression changes that are common to ischemia (modeled by middle cerebral artery occlusion [MCAO]) and to experience-dependent activation (modeled by exposure to an enriched environment [EE]), which also induces Ca2+ transients that trigger transcriptional programs. We found that the activity-dependent transcription factor Npas4 was up-regulated under MCAO and EE conditions and that transient activation of cortical neurons in the healthy brain by the EE decreased cell death after stroke. Furthermore, both MCAO in vivo and oxygen-glucose deprivation in vitro revealed that Npas4 is necessary and sufficient for neuroprotection. We also found that this protection involves the inhibition of L-type voltage-gated Ca2+ channels (VGCCs). Next, our systematic search for Npas4-downstream genes identified Gem, which encodes a Ras-related small GTPase that mediates neuroprotective effects of Npas4. Gem suppresses the membrane localization of L-type VGCCs to inhibit excess Ca2+ influx, thereby protecting neurons from excitotoxic death after in vitro and in vivo ischemia. Collectively, our findings indicate that Gem expression via Npas4 is necessary and sufficient to promote neuroprotection in the injured brain. Importantly, Gem is also induced in human cerebral organoids cultured under an ischemic condition, revealing Gem as a new target for drug discovery.

scholarly journals Temporal Precision of Spike Trains in Extrastriate Cortex of the Behaving Macaque Monkey

1996 ◽  
Vol 8 (6) ◽  
pp. 1185-1202 ◽  
Author(s):  
Wyeth Bair ◽  
Christof Koch
Keyword(s):  
Cortical Neurons ◽  
Action Potentials ◽  
Cortical Area ◽  
Macaque Monkey ◽  
Spike Trains ◽  
Random Motion ◽  
Extrastriate Cortex ◽  
Temporal Modulation ◽  
Temporal Precision ◽  
Neuronal Excitation

How reliably do action potentials in cortical neurons encode information about a visual stimulus? Most physiological studies do not weigh the occurrences of particular action potentials as significant but treat them only as reflections of average neuronal excitation. We report that single neurons recorded in a previous study by Newsome et al. (1989; see also Britten et al. 1992) from cortical area MT in the behaving monkey respond to dynamic and unpredictable motion stimuli with a markedly reproducible temporal modulation that is precise to a few milliseconds. This temporal modulation is stimulus dependent, being present for highly dynamic random motion but absent when the stimulus translates rigidly.

scholarly journals Altered Biosynthesis of Neuropeptide Processing Enzyme Carboxypeptidase E after Brain Ischemia: Molecular Mechanism and Implication

2004 ◽  
Vol 24 (6) ◽  
pp. 612-622 ◽  
Author(s):  
An Zhou ◽  
Manabu Minami ◽  
Xiaoman Zhu ◽  
Sylvia Bae ◽  
John Minthorne ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Brain Ischemia ◽  
Cortical Neurons ◽  
Focal Cerebral Ischemia ◽  
Proteolytic Processing ◽  
Carboxypeptidase E ◽  
Processing Enzyme ◽  
The Impact

In this study, using both in vivo and in vitro ischemia models, the authors investigated the impact of brain ischemia on the biosynthesis of a key neuropeptide-processing enzyme, carboxypeptidase E (CPE). The response to brain ischemia of animals that lacked an active CPE was also examined. Combined in situ hybridization and immunocytochemical analyses for CPE showed reciprocal changes of CPE mRNA and protein, respectively, in the same cortical cells in rat brains after focal cerebral ischemia. Western blot analysis revealed an accumulation of the precursor protein of CPE in the ischemic cortex in vivo and in ischemic cortical neurons in vitro. Detailed metabolic labeling experiments on ischemic cortical neurons showed that ischemic stress caused a blockade in the proteolytic processing of CPE. When mice lacking an active CPE protease were subjected to a sublethal episode of focal cerebral ischemia, abundant TUNEL-positive cells were seen in the ischemic cortex whereas only a few were seen in the cortex of wild-type animals. These findings suggest that ischemia has an adverse impact on the neuropeptide-processing system in the brain and that the lack of an active neuropeptide-processing enzyme exacerbates ischemic brain injury.

scholarly journals Molecular Mechanisms of Neurotransmitter Release Control Distinct Features of Sensory Coding Reliability

2021 ◽  
Author(s):  
Eyal Rozenfeld ◽  
Nadine Ehmann ◽  
Julia E. Manoim ◽  
Robert J. Kittel ◽  
Moshe Parnas
Keyword(s):  
Neurotransmitter Release ◽  
Action Potentials ◽  
Neural Coding ◽  
Information Transfer ◽  
Molecular Mechanisms ◽  
Neural Code ◽  
Temporal Coding ◽  
Neural Representation ◽  
Major Mechanism

AbstractA key requirement for the repeated identification of a stimulus is a reliable neural representation each time it is encountered. Neural coding is often considered to rely on two major coding schemes: the firing rate of action potentials, known as rate coding, and the precise timing of action potentials, known as temporal coding. Synaptic transmission is the major mechanism of information transfer between neurons. While theoretical studies have examined the effects of neurotransmitter release probability on neural code reliability, it has not yet been addressed how different components of the release machinery affect coding of physiological stimuli in vivo. Here, we use the first synapse of the Drosophila olfactory system to show that the reliability of the neural code is sensitive to perturbations of specific presynaptic proteins controlling distinct stages of neurotransmitter release. Notably, the presynaptic manipulations decreased coding reliability of postsynaptic neurons only at high odor intensity. We further show that while the reduced temporal code reliability arises from monosynaptic effects, the reduced rate code reliability arises from circuit effects, which include the recruitment of inhibitory local neurons. Finally, we find that reducing neural coding reliability decreases behavioral reliability of olfactory stimulus classification.

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