Neuronal PAS domain 1 identifies a major subpopulation of wakefulness-promoting GABAergic neurons in basal forebrain DOI Open Access
Timothy A. Troppoli, Chun Yang, Fumi Katsuki

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 11, 2023

ABSTRACT Here we describe a novel group of basal forebrain (BF) neurons expressing neuronal PAS domain 1 (Npas1), developmental transcription factor linked to neuropsychiatric disorders. Immunohistochemical staining in Npas1-cre-2A-TdTomato mice revealed BF Npas1 + are distinct from well-studied parvalbumin or cholinergic neurons. GAD67-GFP knock-in confirmed that the vast majority GABAergic, with minimal colocalization glutamatergic vGlut1-cre-tdTomato vGlut2-cre-tdTomato mice. The density was high, 5-6 times neighboring cholinergic, Anterograde tracing identified prominent projections brain regions involved sleep-wake control, motivated behaviors and olfaction such as lateral hypothalamus, habenula, nucleus accumbens shell, ventral tegmental area olfactory bulb. Chemogenetic activation light (inactive) period increased amount wakefulness latency sleep for 2-3 hr, due an increase long wake bouts short NREM bouts. Non-REM slow-wave (0-1.5 Hz) sigma (9-15 power, well spindle density, amplitude duration, were reduced, reminiscent findings several Together previous implicating stress responsiveness, anatomical effect activating them suggest possible role motivationally-driven stress-induced insomnia. Identification this major subpopulation GABAergic will facilitate studies their disorders, dementia other conditions involving BF. SIGNIFICANCE STATEMENT We characterize mouse subset more numerous than glutamate target areas arousal, motivation olfaction. Activation slow waves spindles reduced wake-promoting allow insomnia,

Language: Английский

Olfactory Critical Periods: How Odor Exposure Shapes the Developing Brain in Mice and Flies DOI Creative Commons
Ahana Mallick, Andrew M. Dacks, Quentin Gaudry

et al.

Biology, Journal Year: 2024, Volume and Issue: 13(2), P. 94 - 94

Published: Feb. 2, 2024

Neural networks have an extensive ability to change in response environmental stimuli. This flexibility peaks during restricted windows of time early life called critical periods. The ubiquitous occurrence this form plasticity across sensory modalities and phyla speaks the importance periods for proper neural development function. Extensive investigation into visual has advanced our knowledge molecular events key processes that underlie impact early-life experience on neuronal plasticity. However, despite olfaction overall survival organism, cellular basis olfactory not garnered study compared Recent work providing a comprehensive mapping highly organized neuropil its turn attracted growing interest how these circuits undergo Here, we perform comparative review fruit flies mice provide novel insight odor exposure shaping highlighting mechanisms found modalities.

Language: Английский

Citations

8

Circuit formation and sensory perception in the mouse olfactory system DOI Creative Commons
Kensaku Mori, Hitoshi Sakano

Frontiers in Neural Circuits, Journal Year: 2024, Volume and Issue: 18

Published: Feb. 16, 2024

In the mouse olfactory system, odor information is converted to a topographic map of activated glomeruli in bulb (OB). Although arrangement genetically determined, glomerular structure plastic and can be modified by environmental stimuli. If pups are exposed particular odorant, responding become larger recruiting dendrites connecting projection neurons interneurons. This imprinting not only increases sensitivity odor, but also imposes positive quality on imprinted memory. External represented as an OB transmitted cortex (OC) amygdala for decision making elicit emotional behavioral outputs using two distinct neural pathways, innate learned. Innate circuits start work right after birth, whereas learned functional later on. this paper, recent progress will summarized study circuit formation perception mice. We propose new hypotheses timing gating activity relation respiration cycle.

Language: Английский

Citations

6

Lactate activates hypothalamic POMC neurons by intercellular signaling DOI Creative Commons
Patricio Órdenes, Pablo S. Villar, Estefanía Tarifeño-Saldivia

et al.

Scientific Reports, Journal Year: 2021, Volume and Issue: 11(1)

Published: Nov. 4, 2021

Previous studies indicate that the activity of hypothalamic POMC neurons can be regulated by glucose via intracellular mechanisms, but its regulation lactate is poorly understood. In addition to energetic role, acts as a signaling molecule. this study, we evaluated function and location receptor, hydroxycarboxylic acid receptor 1 (HCAR1). We used conditional genetic approach label their sensitivity using patch-clamp recordings. L-Lactate 3-chloro-5-hydroxybenzoic (3Cl-HBA), HCAR1 specific agonist depolarized increase in excitability was abolished pertussis toxin (PTX), indicating involvement Gαi/o-protein-coupled receptors. addition, depolarization subset sensitive α-cyano-4-hydroxycinnamate (4-CIN), transporter blocker, suggesting induced L-lactate also occur direct action. Surprisingly, not detected neurons, instead localized astrocytes. These results suggest new lactate-mediated mechanism for astrocyte-neuron intercellular communication.

Language: Английский

Citations

31

Shank3 Deficiency Results in a Reduction in GABAergic Postsynaptic Puncta in the Olfactory Brain Areas DOI Creative Commons
Denisa Mihalj, Veronika Borbélyová, Zdeno Pirník

et al.

Neurochemical Research, Journal Year: 2024, Volume and Issue: 49(4), P. 1008 - 1016

Published: Jan. 6, 2024

Abstract Dysfunctional sensory systems, including altered olfactory function, have recently been reported in patients with autism spectrum disorder (ASD). Disturbances processing can potentially result from gamma-aminobutyric acid (GABA)ergic synaptic abnormalities. The specific molecular mechanism by which GABAergic transmission affects the system ASD remains unclear. Therefore, present study aimed to evaluate selected components of brain regions and primary neurons isolated Shank3 -deficient ( −/− ) mice, are known for their autism-like behavioral phenotype. deficiency led a significant reduction GEPHYRIN/GABA A R colocalization piriform cortex bulb, while no change cell morphology was observed. Gene expression analysis revealed mRNA levels GABA transporter 1 bulb Collybistin frontal mice compared WT mice. similar trend observed Somatostatin other neurotransmission markers did not yield statistically results. Overall, it appears that leads changes synapses important information processing, may represent basis understanding functional impairments autism.

Language: Английский

Citations

3

Target-specific control of olfactory bulb periglomerular cells by GABAergic and cholinergic basal forebrain inputs DOI Creative Commons
Didier De Saint Jan

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Feb. 28, 2022

The olfactory bulb (OB), the first relay for odor processing in brain, receives dense GABAergic and cholinergic long-range projections from basal forebrain (BF) nuclei that provide information about internal state behavioral context of animal. However, targets, impact, dynamic these afferents are still unclear. How BF synaptic inputs modulate activity diverse subtypes periglomerular (PG) interneurons using optogenetic stimulation loose cell-attached or whole-cell patch-clamp recording OB slices adult mice were studied this article. potently blocked PG cells firing except a minority calretinin-expressing which GABA release elicited spiking. Parallel excited previously overlooked cell subtype via activation M1 muscarinic receptors. Low-frequency axons drove persistent cells, thereby increasing tonic inhibition principal neurons. Taken together, findings suggest modality-specific can orchestrate glomeruli multiple, potentially independent, inhibitory excitatory target-specific pathways.

Language: Английский

Citations

15

GABAA receptors in epilepsy: Elucidating phenotypic divergence through functional analysis of genetic variants DOI Creative Commons
Nathan L. Absalom, Susan X. N. Lin, Vivian W. Y. Liao

et al.

Journal of Neurochemistry, Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 24, 2023

Abstract Normal brain function requires a tightly regulated balance between excitatory and inhibitory neurotransmissions. γ‐Aminobutyric acid type A (GABA ) receptors represent the major class of ion channels in mammalian brain. Dysregulation these and/or their associated pathways is strongly implicated pathophysiology epilepsy. To date, hundreds different GABA receptor subunit variants have been with epilepsy, making them prominent cause genetically linked While identifying genetic crucial for accurate diagnosis effective counselling, it does not necessarily lead to improved personalised treatment options. This because identification variant reveal how affected. Genetic subunits can complex changes properties resulting various degrees gain‐of‐function, loss‐of‐function or combination both. Understanding affect therefore represents an important first step ongoing development precision therapies. Furthermore, ensure that functional data are produced using methodologies allow be classified clinical guidelines such as those developed by American College Medical Genetics Genomics. article will review current knowledge field provide recommendations future analysis variants. image

Language: Английский

Citations

8

Dynamic Cholinergic Tone in the Basal Forebrain Reflects Reward-Seeking and Reinforcement During Olfactory Behavior DOI Creative Commons

Elizabeth Hanson,

Katie L. Brandel-Ankrapp, Benjamin R. Arenkiel

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: Feb. 2, 2021

Sensory perception underlies how we internalize and interact with the external world. In order to adapt changing circumstances interpret signals in a variety of contexts, sensation needs be reliable, but sensory input flexible. An important mediator this flexibility is top-down regulation from cholinergic basal forebrain. Basal forebrain projection neurons serve as pacemakers gatekeepers for downstream neural networks, modulating circuit activity across diverse neuronal populations. This control necessary cue detection, learning, memory, disproportionately disrupted neurodegenerative diseases associated cognitive decline. Intriguingly, signaling acts locally within sculpt output neurons. To determine local impacts pathways that participate regulation, sought define dynamics during motivated behavior learning. Toward this, utilized fiber photometry genetically encoded acetylcholine indicator GAChR2.0 temporal patterns olfactory-guided, behaviors We show reliably increased reward seeking behaviors, was strongly suppressed by delivery go/no-go olfactory-cued discrimination task. The observed transient reduction tone mirrored suppression GABAergic activity. Together, these findings suggest changes rapidly reflect reward-seeking positive reinforcement may impact circuitry modulates olfaction.

Language: Английский

Citations

20

Long-range GABAergic projections contribute to cortical feedback control of sensory processing DOI Creative Commons
Camille Mazo, Antoine Nissant, Soham Saha

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Nov. 12, 2022

Abstract In the olfactory system, cortex sends glutamatergic projections back to first stage of processing, bulb (OB). Such corticofugal excitatory circuits — a canonical circuit motif described in all sensory systems— dynamically adjust early processing. Here, we uncover inhibitory feedback OB, originating from subpopulation GABAergic neurons anterior and innervating both local output OB neurons. vivo imaging network modeling showed that optogenetic activation cortical drives net subtractive inhibition spontaneous odor-evoked activity as well neurons, stimulation enhances separation population odor responses tufted cells, but not mitral cells. Targeted pharmacogenetic silencing axon terminals impaired discrimination similar mixtures. Thus, represent an additional control

Language: Английский

Citations

10

Frequency-dependent centrifugal modulation of the activity of different classes of mitral and tufted cells in olfactory bulb DOI
Fu‐Wen Zhou,

Chelsea Hook,

Adam C. Puché

et al.

Journal of Neurophysiology, Journal Year: 2023, Volume and Issue: 129(6), P. 1515 - 1533

Published: May 24, 2023

Neuronal circuits in the olfactory bulb closely modulate output activity. Activation of GABAergic from HDB to has both direct and indirect action differentially across five classes M/TC bulbar neurons. The net effect enhances excitability deeper neurons as frequency increases, altering relative inhibition-excitation balance circuits. We hypothesize that this sharpens tuning specificity M/TCs odors during sensory processing.

Language: Английский

Citations

3

Single-cell reconstruction reveals input patterns and pathways into corticotropin-releasing factor neurons in the central amygdala in mice DOI Creative Commons
Chuan Huang, Yu Wang, Peng Chen

et al.

Communications Biology, Journal Year: 2022, Volume and Issue: 5(1)

Published: April 6, 2022

Abstract Corticotropin-releasing factor (CRF) neurons are one of the most densely distributed cell types in central amygdala (CeA), and involved a wide range behaviors including anxiety learning. However, fundamental input circuits patterns CeA-CRF still unclear. Here, we generate monosynaptic-input map onto at single-cell resolution via retrograde rabies-virus system. We find all inputs located 44 nested subregions that directly innervate neurons; them top-down convergent expressing Ca 2+ /calmodulin-dependent protein kinase II, centralized cortex, especially layer 4 somatosensory which may relay information from thalamus. While bottom-up divergent have highest proportion glutamate decarboxylase expression. Finally, en passant structures single neuron revealed by in-situ reconstruction modified 3D-reference atlas, represented Periaqueductal gray-Subparafascicular nucleus-Subthalamic nucleus-Globus pallidus-Caudoputamen-CeA pathway. Taken together, our findings provide morphological connectivity properties neurons, insights for future studies interrogating circuit mechanisms mediating various functions.

Language: Английский

Citations

4