Npas4: Linking Neuronal Activity to Memory

Sun, Xiaochen; Lin, Yingxi

doi:10.1016/j.tins.2016.02.003

Cited by 163 publications

(160 citation statements)

References 79 publications

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“…Since different IEGs have unique induction profiles in different cell-types (38, 67, 68), it is critical to characterize IEG expression profiles for brain regions of interest before beginning experiments. With IEG promoters driving reporters to visualize activated neurons, the design of the transgene may dictate how faithfully the reporter follows activity.…”

Section: Summary and Future Perspectivesmentioning

confidence: 99%

Genetic strategies to access activated neurons

DeNardo

Luo

2017

Current Opinion in Neurobiology

126

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A major goal of modern neuroscience is to understand how ensembles of neurons participate in neural circuits underlying behavior. The recent explosion of genetically-encoded circuit analysis tools has allowed neuroscientists to characterize molecularly-defined neuronal types with unprecedented detail. However, since neurons defined by molecular expression can be functionally heterogeneous, targeting circuit analysis tools to neurons based on their activity is critical to elucidating the neural basis of behavior. Here we review genetic strategies to access activated neurons and characterize their functional properties, molecular profiles, connectivity, and causal roles in sensory-coding, memory, and valence-encoding. We also discuss future possibilities for improving these strategies and using them to screen brain-wide activity patterns underlying adaptive and maladaptive behaviors.

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Section: Summary and Future Perspectivesmentioning

confidence: 99%

Genetic strategies to access activated neurons

DeNardo

Luo

2017

Current Opinion in Neurobiology

126

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“…By regulating the number of inhibitory synapses onto excitatory cells, Npas4 is critical in limiting the amount of excitation that results from stimulation . In rodent models of decreased Npas4 expression, the resulting imbalance in cortical excitation leads to several disease‐relevant behavioral outcomes including: hyperactivity, seizures, social anxiety, contextual memory impairment and increased vulnerability to stress …”

Section: Introductionmentioning

confidence: 99%

Npas4 deficiency and prenatal stress interact to affect social recognition in mice

Heslin

Coutellier

2018

Genes Brain and Behavior

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Neurodevelopmental disorders such as autism spectrum disorders and schizophrenia have an expansive array of reported genetic and environmental contributing factors. However, none of these factors alone can account for a substantial proportion of cases of either disorder. Instead, many gene-by-environment interactions are responsible for neurodevelopmental disturbances that lead to these disorders. The current experiment used heterozygous knock-out mice to examine a potential interaction between 2 factors commonly linked to neurodevelopmental disorders and cognitive deficit: imbalanced excitatory/inhibitory signaling in the cortex and prenatal stress (PNS) exposure. Both of these factors have been linked to disrupt GABAergic signaling in the prefrontal cortex (PFC), a common feature of neurodevelopmental disorders. The neuronal PAS domain protein 4 (Npas4) gene is instrumental in regulation of the excitatory/inhibitory balance in the cortex and hippocampus in response to activation. Npas4 heterozygous and wild-type male and female mice were exposed to either PNS or standard gestation, then evaluated during adulthood in social and anxiety behavioral measures. The combination of PNS and Npas4 deficiency in male mice impaired social recognition. This behavioral deficit was associated with decreased parvalbumin and cFos protein expression in the infralimbic region of the PFC following social stimulation in Npas4 heterozygous males. In contrast, females displayed fewer behavioral effects and molecular changes in PFC in response to PNS and decreased Npas4.

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“…While this perspective article has focused on the role of Arc in glutamatergic and DA signaling in frontal cortex as a well-characterized model for activity-dependent genetic feedback, recent studies have also provided exciting insights into the functions of other IEGs in both excitatory and inhibitory neuronal circuits (Leslie and Nedivi, 2011; Sun and Lin, 2016). Particularly, it has been reported that neuronal activity induces distinctive gene expression programs in excitatory and inhibitory neurons (Spiegel et al, 2014; Mardinly et al, 2016).…”

Section: Resultsmentioning

confidence: 99%

Genetic Feedback Regulation of Frontal Cortical Neuronal Ensembles Through Activity-Dependent Arc Expression and Dopaminergic Input

Mastwal

Cao

Wang

2016

Front. Neural Circuits

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Mental functions involve coordinated activities of specific neuronal ensembles that are embedded in complex brain circuits. Aberrant neuronal ensemble dynamics is thought to form the neurobiological basis of mental disorders. A major challenge in mental health research is to identify these cellular ensembles and determine what molecular mechanisms constrain their emergence and consolidation during development and learning. Here, we provide a perspective based on recent studies that use activity-dependent gene Arc/Arg3.1 as a cellular marker to identify neuronal ensembles and a molecular probe to modulate circuit functions. These studies have demonstrated that the transcription of Arc is activated in selective groups of frontal cortical neurons in response to specific behavioral tasks. Arc expression regulates the persistent firing of individual neurons and predicts the consolidation of neuronal ensembles during repeated learning. Therefore, the Arc pathway represents a prototypical example of activity-dependent genetic feedback regulation of neuronal ensembles. The activation of this pathway in the frontal cortex starts during early postnatal development and requires dopaminergic (DA) input. Conversely, genetic disruption of Arc leads to a hypoactive mesofrontal dopamine circuit and its related cognitive deficit. This mutual interaction suggests an auto-regulatory mechanism to amplify the impact of neuromodulators and activity-regulated genes during postnatal development. Such a mechanism may contribute to the association of mutations in dopamine and Arc pathways with neurodevelopmental psychiatric disorders. As the mesofrontal dopamine circuit shows extensive activity-dependent developmental plasticity, activity-guided modulation of DA projections or Arc ensembles during development may help to repair circuit deficits related to neuropsychiatric disorders.

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Npas4: Linking Neuronal Activity to Memory

Cited by 163 publications

References 79 publications

Genetic strategies to access activated neurons

Genetic strategies to access activated neurons

Npas4 deficiency and prenatal stress interact to affect social recognition in mice

Genetic Feedback Regulation of Frontal Cortical Neuronal Ensembles Through Activity-Dependent Arc Expression and Dopaminergic Input

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