scholarly journals Corticostriatal stimulation compensates for medial frontal inactivation during interval timing

2019 ◽  
Author(s):  
Eric B. Emmons ◽  
Morgan Kennedy ◽  
Youngcho Kim ◽  
Nandakumar S. Narayanan
Keyword(s):  
Working Memory ◽  
Temporal Processing ◽  
Response Times ◽  
Interval Timing ◽  
Brain Diseases ◽  
Axon Terminals ◽  
Optogenetic Stimulation ◽  
Prefrontal Dysfunction ◽  
Timing Task ◽  
Stimulation Of

AbstractPrefrontal dysfunction is a common feature of brain diseases such as schizophrenia and contributes to deficits in executive functions, including working memory, attention, flexibility, inhibitory control, and timing of behaviors. Currently, few interventions can compensate for impaired prefrontal function. Here, we tested whether stimulating the axons of prefrontal neurons in the striatum could compensate for deficits in temporal processing related to prefrontal dysfunction. We used an interval-timing task that requires working memory for temporal rules and attention to the passage of time. Our previous work showed that inactivation of the medial frontal cortex (MFC) impairs interval timing and attenuates ramping activity, a key form of temporal processing in the dorsomedial striatum (DMS). We found that 20-Hz optogenetic stimulation of MFC axon terminals in the DMS shifted response times and improved interval-timing behavior. Furthermore, optogenetic stimulation of terminals modulated time-related ramping of medium spiny neurons in the striatum. These data suggest that corticostriatal stimulation can compensate for deficits caused by MFC inactivation and they imply that frontostriatal projections are sufficient for controlling responses in time.

scholarly journals Corticostriatal stimulation compensates for medial frontal inactivation during interval timing

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Eric B. Emmons ◽  
Morgan Kennedy ◽  
Youngcho Kim ◽  
Nandakumar S. Narayanan
Keyword(s):  
Working Memory ◽  
Temporal Processing ◽  
Interval Timing ◽  
Brain Diseases ◽  
Axon Terminals ◽  
Optogenetic Stimulation ◽  
Prefrontal Function ◽  
Prefrontal Dysfunction ◽  
Timing Task ◽  
Stimulation Of

Abstract Prefrontal dysfunction is a common feature of brain diseases such as schizophrenia and contributes to deficits in executive functions, including working memory, attention, flexibility, inhibitory control, and timing of behaviors. Currently, few interventions improve prefrontal function. Here, we tested whether stimulating the axons of prefrontal neurons in the striatum could compensate for deficits in temporal processing related to prefrontal dysfunction. We used an interval-timing task that requires working memory for temporal rules and attention to the passage of time. Our previous work showed that inactivation of the medial frontal cortex (MFC) impairs interval timing and attenuates ramping activity, a key form of temporal processing in the dorsomedial striatum (DMS). We found that 20-Hz optogenetic stimulation of MFC axon terminals increased curvature of time-response histograms and improved interval-timing behavior. Furthermore, optogenetic stimulation of terminals modulated time-related ramping of medium spiny neurons in the striatum. These data suggest that corticostriatal stimulation can compensate for deficits caused by MFC inactivation and they imply that frontostriatal projections are sufficient for controlling responses in time.

scholarly journals Medial frontal ∼4-Hz activity in humans and rodents is attenuated in PD patients and in rodents with cortical dopamine depletion

2015 ◽  
Vol 114 (2) ◽  
pp. 1310-1320 ◽  
Author(s):  
Krystal L. Parker ◽  
Kuan-Hua Chen ◽  
Johnathan R. Kingyon ◽  
James F. Cavanagh ◽  
Nandakumar S. Narayanan
Keyword(s):  
Executive Function ◽  
Temporal Processing ◽  
Spectral Power ◽  
Low Frequency ◽  
Interval Timing ◽  
Theta Activity ◽  
Functional Coupling ◽  
Rodent Models ◽  
Dopamine Depletion ◽  
Timing Task

The temporal control of action is a highly conserved and critical mammalian behavior. Here, we investigate the neuronal basis of this process using an interval timing task. In rats and humans, instructional timing cues triggered spectral power across delta and theta bands (2–6 Hz) from the medial frontal cortex (MFC). Humans and rodents with dysfunctional dopamine have impaired interval timing, and we found that both humans with Parkinson's disease (PD) and rodents with local MFC dopamine depletion had attenuated delta and theta activity. In rodents, spectral activity in this range could functionally couple single MFC neurons involved in temporal processing. Without MFC dopamine, these neurons had less functional coupling with delta/theta activity and less temporal processing. Finally, in humans this 2- to 6-Hz activity was correlated with executive function in matched controls but not in PD patients. Collectively, these findings suggest that cue-evoked low-frequency rhythms could be a clinically important biomarker of PD that is translatable to rodent models, facilitating mechanistic inquiry and the development of neurophysiological biomarkers for human disease.

scholarly journals Optogenetic stimulation of long-range inputs and functional characterization of connectivity in patch-clamp recordings in mouse brain slices

2018 ◽  
Author(s):  
Louis Richevaux ◽  
Louise Schenberg ◽  
Mathieu Beraneck ◽  
Desdemona Fricker
Keyword(s):  
Patch Clamp ◽  
Long Range ◽  
Brain Slices ◽  
Cell Type ◽  
Patch Clamp Recording ◽  
Axon Terminals ◽  
Optogenetic Stimulation ◽  
Cell Type Specific ◽  
The Brain ◽  
Stimulation Of

Knowledge of cell type specific synaptic connectivity is a crucial prerequisite for understanding brain wide neuronal circuits. The functional investigation of long-range connections requires targeted recordings of single neurons combined with the specific stimulation of identified distant inputs. This is often difficult to achieve with conventional, electrical stimulation techniques, because axons from converging upstream brain areas may intermingle in the target region. The stereotaxic targeting of a specific brain region for virus-mediated expression of light sensitive ion channels allows to selectively stimulate axons coming from that region with light. Intracerebral stereotaxic injections can be used in well-delimited structures, such as the anterodorsal thalamic nuclei, and also in other subcortical or cortical areas throughout the brain. Here we describe a set of techniques for precise stereotaxic injection of viral vectors expressing channelrhodopsin in the anterodorsal thalamus, followed by photostimulation of their axon terminals in hippocampal slices. In combination with whole-cell patch clamp recording from a postsynaptically connected presubicular neuron, photostimulation of thalamic axons allows the detection of functional synaptic connections, their pharmacological characterization, and the evaluation of their strength in the brain slice preparation. We demonstrate that axons originating in the anterodorsal thalamus ramify densely in presubicular layers 1 and 3. The photostimulation of Chronos expressing thalamic axon terminals in presubiculum initiates short latency postsynaptic responses in a presubicular layer3 neuron, indicating a monosynaptic connection. In addition, biocytin filling of the recorded neuron and posthoc revelation confirms the layer localization and pyramidal morphology of the postsynaptic neuron. Taken together, the optogenetic stimulation of long-range inputs in ex vivo brain slices is a useful method to determine the cell-type specific functional connectivity from distant brain regions.

scholarly journals Delta Frequency Optogenetic Stimulation of the Thalamic Nucleus Reuniens Is Sufficient to Produce Working Memory Deficits: Relevance to Schizophrenia

2015 ◽  
Vol 77 (12) ◽  
pp. 1098-1107 ◽  
Author(s):  
Aranda R. Duan ◽  
Carmen Varela ◽  
Yuchun Zhang ◽  
Yinghua Shen ◽  
Lealia Xiong ◽  
...  
Keyword(s):  
Working Memory ◽  
Thalamic Nucleus ◽  
Memory Deficits ◽  
Nucleus Reuniens ◽  
Optogenetic Stimulation ◽  
Stimulation Of

scholarly journals Experiential and Strategic Emotional Intelligence Are Implicated When Inhibiting Affective and Non-Affective Distractors: Findings from Three Emotional Flanker N-Back Tasks

2021 ◽  
Vol 9 (1) ◽  
pp. 12
Author(s):  
Ming D. Lim ◽  
Damian P. Birney
Keyword(s):  
Working Memory ◽  
Emotional Intelligence ◽  
Experimental Evidence ◽  
Cognitive Processes ◽  
Response Times ◽  
Memory Task ◽  
Low Load ◽  
Affective Information ◽  
Accuracy Rates

Emotional intelligence (EI) refers to a set of competencies to process, understand, and reason with affective information. Recent studies suggest ability measures of experiential and strategic EI differentially predict performance on non-emotional and emotionally laden tasks. To explore cognitive processes underlying these abilities further, we varied the affective context of a traditional letter-based n-back working-memory task. In study 1, participants completed 0-, 2-, and 3-back tasks with flanking distractors that were either emotional (fearful or happy faces) or non-emotional (shapes or letters stimuli). Strategic EI, but not experiential EI, significantly influenced participants’ accuracy across all n-back levels, irrespective of flanker type. In Study 2, participants completed 1-, 2-, and 3-back levels. Experiential EI was positively associated with response times for emotional flankers at the 1-back level but not other levels or flanker types, suggesting those higher in experiential EI reacted slower on low-load trials with affective context. In Study 3, flankers were asynchronously presented either 300 ms or 1000 ms before probes. Results mirrored Study 1 for accuracy rates and Study 2 for response times. Our findings (a) provide experimental evidence for the distinctness of experiential and strategic EI and (b) suggest that each are related to different aspects of cognitive processes underlying working memory.

scholarly journals Incerto-thalamic modulation of fear via GABA and dopamine

2021 ◽  
Author(s):  
Archana Venkataraman ◽  
Sarah C. Hunter ◽  
Maria Dhinojwala ◽  
Diana Ghebrezadik ◽  
JiDong Guo ◽  
...  
Keyword(s):  
Brain Regions ◽  
Zona Incerta ◽  
Dependent Manner ◽  
Post Traumatic Stress ◽  
Functional Roles ◽  
Functional Connections ◽  
Optogenetic Stimulation ◽  
Fear Generalization ◽  
Stimulation Of

AbstractFear generalization and deficits in extinction learning are debilitating dimensions of Post-Traumatic Stress Disorder (PTSD). Most understanding of the neurobiology underlying these dimensions comes from studies of cortical and limbic brain regions. While thalamic and subthalamic regions have been implicated in modulating fear, the potential for incerto-thalamic pathways to suppress fear generalization and rescue deficits in extinction recall remains unexplored. We first used patch-clamp electrophysiology to examine functional connections between the subthalamic zona incerta and thalamic reuniens (RE). Optogenetic stimulation of GABAergic ZI → RE cell terminals in vitro induced inhibitory post-synaptic currents (IPSCs) in the RE. We then combined high-intensity discriminative auditory fear conditioning with cell-type-specific and projection-specific optogenetics in mice to assess functional roles of GABAergic ZI → RE cell projections in modulating fear generalization and extinction recall. In addition, we used a similar approach to test the possibility of fear generalization and extinction recall being modulated by a smaller subset of GABAergic ZI → RE cells, the A13 dopaminergic cell population. Optogenetic stimulation of GABAergic ZI → RE cell terminals attenuated fear generalization and enhanced extinction recall. In contrast, optogenetic stimulation of dopaminergic ZI → RE cell terminals had no effect on fear generalization but enhanced extinction recall in a dopamine receptor D1-dependent manner. Our findings shed new light on the neuroanatomy and neurochemistry of ZI-located cells that contribute to adaptive fear by increasing the precision and extinction of learned associations. In so doing, these data reveal novel neuroanatomical substrates that could be therapeutically targeted for treatment of PTSD.

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