Specialized coding patterns among dorsomedial prefrontal neuronal ensembles during conditioned reward seeking.

Non-overlapping cell populations within dorsomedial prefrontal cortex (dmPFC), defined by gene expression or projection target, control dissociable aspects of reward seeking through unique activity patterns. However, even within these defined cell populations considerable cell-to-cell variability is found, suggesting that greater resolution is needed to understand information processing in dmPFC. Here we use two-photon calcium imaging in awake, behaving mice to monitor the activity of dmPFC excitatory neurons throughout Pavlovian sucrose conditioning. We characterize five unique neuronal ensembles that each encode specialized information related to a reward, reward-predictive cues, and behavioral responses to reward-predictive cues. The ensembles differentially emerge across learning, and stabilize after learning, in a manner that improves the predictive validity of dmPFC activity dynamics for deciphering variables related to behavioral conditioning. Our results characterize the complex dmPFC neuronal ensemble dynamics that relay learning-dependent signals for prediction of reward availability and initiation of conditioned reward seeking.

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Specialized coding patterns among dorsomedial prefrontal neuronal ensembles predict conditioned reward seeking

eLife ◽

10.7554/elife.65764 ◽

2021 ◽

Vol 10 ◽

Author(s):

Roger I Grant ◽

Elizabeth M Doncheck ◽

Kelsey M Vollmer ◽

Kion T Winston ◽

Elizaveta V Romanova ◽

...

Keyword(s):

Activity Patterns ◽

Cell Populations ◽

Conditioned Reward ◽

Neuronal Ensembles ◽

Two Photon ◽

Reward Seeking ◽

Reward Conditioning ◽

Daily Training ◽

Cell To Cell Variability ◽

Reward Availability

Non-overlapping cell populations within dorsomedial prefrontal cortex (dmPFC), defined by gene expression or projection target, control dissociable aspects of reward seeking through unique activity patterns. However, even within these defined cell populations considerable cell-to-cell variability is found, suggesting that greater resolution is needed to understand information processing in dmPFC. Here we use two-photon calcium imaging in awake, behaving mice to monitor the activity of dmPFC excitatory neurons throughout Pavlovian reward conditioning. We characterize five unique neuronal ensembles that each encode specialized information related to a sucrose reward, reward-predictive cues, and behavioral responses to those cues. The ensembles differentially emerge across daily training sessions - and stabilize after learning - in a manner that improves the predictive validity of dmPFC activity dynamics for deciphering variables related to behavioral conditioning. Our results characterize the complex dmPFC neuronal ensemble dynamics that stably predict reward availability and initiation of conditioned reward seeking following cue-reward learning.

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Reduced repertoire of cortical microstates and neuronal ensembles in medically-induced loss of consciousness

10.1101/358168 ◽

2018 ◽

Author(s):

Michael Wenzel ◽

Shuting Han ◽

Elliot H. Smith ◽

Erik Hoel ◽

Bradley Greger ◽

...

Keyword(s):

Complexity Analysis ◽

Human Subjects ◽

Brain Connectivity ◽

Activity Patterns ◽

Field Potential ◽

Electrode Array ◽

Loss Of Consciousness ◽

Population Activity ◽

Neuronal Ensembles ◽

Two Photon

SUMMARYMedically-induced loss of consciousness (mLOC) has been linked to a macroscale break-down of brain connectivity, yet the neural microcircuit correlates of mLOC remain unknown. We applied non-linear t-stochastic neighbor embedding (t-SNE) and Lempel-Ziv-Welch complexity analysis to two-photon calcium imaging and local field potential (LFP) measurements of cortical microcircuit activity across anesthetic depth in mice, and to micro-electrode array recordings in human subjects. We find that mLOC disrupts population activity patterns by i) a reduction of discriminable network microstates and ii) a reduction of independent neuronal ensembles. These alterations are not explained by a simple reduction of neuronal activity and reveal abnormal functional microcircuits. Thus, normal neuronal ensemble dynamics could contribute to the emergence of conscious states.

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Ultrafast Light Targeting for High-Throughput Precise Control of Neuronal Networks

10.1101/2021.06.14.448315 ◽

2021 ◽

Author(s):

Giulia Faini ◽

Clement Molinier ◽

Cecile Telliez ◽

Christophe Tourain ◽

Benoit C Forget ◽

...

Keyword(s):

Single Cell ◽

Activity Patterns ◽

Optical Control ◽

Temporal Control ◽

Precise Control ◽

Neuronal Ensembles ◽

Two Photon ◽

Spatio Temporal ◽

Focused Beams ◽

Ability To Drive

Understanding how specific sets of neurons fire and wire together during cognitive-relevant activity is one of the most pressing questions in neuroscience. Two-photon, single-cell resolution optogenetics based on holographic light-targeting approaches enables accurate spatio-temporal control of individual or multiple neurons. Yet, currently, the ability to drive asynchronous activity in distinct cells is critically limited to a few milliseconds and the achievable number of targets to several dozens. In order to expand the capability of single-cell optogenetics, we introduce an approach capable of ultra-fast sequential light targeting (FLiT), based on switching temporally focused beams between holograms at kHz rates. We demonstrate serial-parallel photostimulation strategies capable of multi-cell sub-millisecond temporal control and many-fold expansion of the number of activated cells. This approach will be important for experiments that require rapid and precise cell stimulation with defined spatio-temporal activity patterns and optical control of large neuronal ensembles.

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Seizures start as silent microseizures by neuronal ensembles

10.1101/358903 ◽

2018 ◽

Author(s):

Michael Wenzel ◽

Jordan P. Hamm ◽

Darcy S. Peterka ◽

Rafael MD Yuste

Keyword(s):

Calcium Imaging ◽

Travelling Wave ◽

Inhibitory Neurons ◽

Neural Activation ◽

Calcium Dynamics ◽

Neuronal Ensembles ◽

Two Photon ◽

Step Model

AbstractUnderstanding seizure formation and spread remains a critical goal of epilepsy research. While many studies have documented seizure spread, it remains mysterious how they start. We used fast in-vivo two-photon calcium imaging to reconstruct, at cellular resolution, the dynamics of focal cortical seizures as they emerge in epileptic foci (intrafocal), and subsequently propagate (extrafocal). We find that seizures start as intrafocal coactivation of small numbers of neurons (ensembles), which are electrographically silent. These silent “microseizures” expand saltatorily until they break into neighboring cortex, where they progress smoothly and first become detectable by LFP. Surprisingly, we find spatially heterogeneous calcium dynamics of local PV interneuron sub-populations, which rules out a simple role of inhibitory neurons during seizures. We propose a two-step model for the circuit mechanisms of focal seizures, where neuronal ensembles first generate a silent microseizure, followed by widespread neural activation in a travelling wave, which is then detected electrophysiologically.

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Activation of Adenosine A2A receptor-containing indirect medium spiny neurons in the dorsomedial striatum reduces ethanol containing conditioned reward seeking

IBRO Reports ◽

10.1016/j.ibror.2019.07.1543 ◽

2019 ◽

Vol 6 ◽

pp. S492

Author(s):

Sa-Ik Hong ◽

Seoungwoo Kang ◽

Jiang-Fan Chen ◽

Doo-Sup Choi

Keyword(s):

Adenosine A2a Receptor ◽

Medium Spiny Neurons ◽

Conditioned Reward ◽

Reward Seeking ◽

Spiny Neurons ◽

A2a Receptor ◽

Adenosine A2a ◽

Dorsomedial Striatum

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In Vivo Calcium Imaging of Neural Network Function

Physiology ◽

10.1152/physiol.00032.2007 ◽

2007 ◽

Vol 22 (6) ◽

pp. 358-365 ◽

Cited By ~ 105

Author(s):

Werner Göbel ◽

Fritjof Helmchen

Keyword(s):

Calcium Imaging ◽

Activity Patterns ◽

Network Activity ◽

Network Function ◽

Two Photon ◽

Calcium Indicators ◽

Recent Developments ◽

In Vivo Calcium Imaging ◽

Function Network

Spatiotemporal activity patterns in local neural networks are fundamental to brain function. Network activity can now be measured in vivo using two-photon imaging of cell populations that are labeled with fluorescent calcium indicators. In this review, we discuss basic aspects of in vivo calcium imaging and highlight recent developments that will help to uncover operating principles of neural circuits.

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Calcium imaging reveals depressive- and manic-phase-specific brain neural activity patterns in a murine model of bipolar disorder: a pilot study

Translational Psychiatry ◽

10.1038/s41398-021-01750-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Min Chen ◽

Hongjun Tian ◽

Guoyong Huang ◽

Tao Fang ◽

Xiaodong Lin ◽

...

Keyword(s):

Bipolar Disorder ◽

Murine Model ◽

Neural Activity ◽

Activity Patterns ◽

Mild Stress ◽

Two Photon ◽

Immobility Time ◽

Photon Imaging ◽

Two Photon Imaging ◽

Depressive Episodes

AbstractBrain pathological features during manic/hypomanic and depressive episodes in the same patients with bipolar disorder (BPD) have not been described precisely. The study aimed to investigate depressive and manic-phase-specific brain neural activity patterns of BPD in the same murine model to provide information guiding investigation of the mechanism of phase switching and tailored prevention and treatment for patients with BPD. In vivo two-photon imaging was used to observe brain activity alterations in the depressive and manic phases in the same murine model of BPD. Two-photon imaging showed significantly reduced Ca2+ activity in temporal cortex pyramidal neurons in the depression phase in mice exposed to chronic unpredictable mild stress (CUMS), but not in the manic phase in mice exposed to CUMS and ketamine. Total integrated calcium values correlated significantly with immobility times. Brain Ca2+ hypoactivity was observed in the depression and manic phases in the same mice exposed to CUMS and ketamine relative to naïve controls. The novel object recognition preference ratio correlated negatively with the immobility time in the depression phase and the total distance traveled in the manic phase. With recognition of its limitations, this study revealed brain neural activity impairment indicating that intrinsic emotional network disturbance is a mechanism of BPD and that brain neural activity is associated with cognitive impairment in the depressive and manic phases of this disorder. These findings are consistent with those from macro-imaging studies of patients with BPD. The observed correlation of brain neural activity with the severity of depressive, but not manic, symptoms need to be investigated further.

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Long-term stability of cortical ensembles

eLife ◽

10.7554/elife.64449 ◽

2021 ◽

Vol 10 ◽

Author(s):

Jesús Pérez-Ortega ◽

Tzitzitlini Alejandre-García ◽

Rafael Yuste

Keyword(s):

Calcium Imaging ◽

Pyramidal Neurons ◽

Evoked Responses ◽

Single Session ◽

Long Term Stability ◽

Neuronal Ensembles ◽

Two Photon ◽

Layer 2 ◽

Over Time

Neuronal ensembles, coactive groups of neurons found in spontaneous and evoked cortical activity, are causally related to memories and perception, but it still unknown how stable or flexible they are over time. We used two-photon multiplane calcium imaging to track over weeks the activity of the same pyramidal neurons in layer 2/3 of the visual cortex from awake mice and recorded their spontaneous and visually evoked responses. Less than half of the neurons were commonly active across any two imaging sessions. These 'common neurons' formed stable ensembles lasting weeks, but some ensembles were also transient and appeared only in one single session. Stable ensembles preserved ~68 % of their neurons up to 46 days, our longest imaged period, and these 'core' cells had stronger functional connectivity. Our results demonstrate that neuronal ensembles can last for weeks and could, in principle, serve as a substrate for long-lasting representation of perceptual states or memories.

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