Lights, fiber, action! A primer on in vivo fiber photometry

Neuron, Journal Year: 2023, Volume and Issue: 112(5), P. 718 - 739

Published: Dec. 15, 2023

Fiber photometry is a key technique for characterizing brain-behavior relationships in vivo. Initially, it was primarily used to report calcium dynamics as proxy neural activity via genetically encoded indicators. This generated new insights into brain functions including movement, memory, and motivation at the level of defined circuits cell types. Recently, opportunity discovery with fiber has exploded development an extensive range fluorescent sensors biomolecules neuromodulators peptides that were previously inaccessible critical advance, combined availability affordable "plug-and-play" recording systems, made monitoring molecules high spatiotemporal precision during behavior highly accessible. However, while opening exciting avenues research, rapid expansion applications occurred without coordination or consensus on best practices. Here, we provide comprehensive guide help end-users execute, analyze, suitably interpret studies.

Language: Английский

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Dopamine transients follow a striatal gradient of reward time horizons

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(4), P. 737 - 746

Published: Feb. 6, 2024

Abstract Animals make predictions to guide their behavior and update those through experience. Transient increases in dopamine (DA) are thought be critical signals for updating predictions. However, it is unclear how this mechanism handles a wide range of behavioral timescales—from seconds or less (for example, if singing song) potentially hours more hunting food). Here we report that DA transients distinct rat striatal subregions convey prediction errors based on time horizons. dynamics systematically accelerated from ventral dorsomedial dorsolateral striatum, the tempo spontaneous fluctuations, temporal integration prior rewards discounting future rewards. This spectrum timescales evaluative computations can help achieve efficient learning adaptive motivation broad behaviors.

Language: Английский

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Enhanced motivated behavior mediated by pharmacological targeting of the FGF14/Nav1.6 complex in nucleus accumbens neurons

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Protein/protein interactions (PPI) play crucial roles in neuronal functions. Yet, their potential as drug targets for brain disorders remains underexplored. The fibroblast growth factor 14 (FGF14)/voltage-gated Na+ channel 1.6 (Nav1.6) complex regulates excitability of medium spiny neurons (MSN) the nucleus accumbens (NAc), a central hub reward circuitry that controls motivated behaviors. Here, we identified compound 1028 (IUPAC: ethyl 3-(2-(3-(hydroxymethyl)-1H-indol-1-yl)acetamido)benzoate), brain-permeable small molecule FGF14R117, critical residue located within druggable pocket at FGF14/Nav1.6 PPI interface. We found modulates assembly and depolarizes voltage-dependence Nav1.6 inactivation with nanomolar potency by modulating intramolecular interaction between III-IV linker C-terminal domain channel. Consistent compound's effects on inactivation, enhances MSN ex vivo accumbal neuron firing rate murine models. Systemic administration maintains behavioral motivation preferentially during motivationally deficient conditions These were abrogated gene silencing Fgf14 NAc accompanied selective reduction dopamine levels consumption findings underscore to selectively regulate behaviors associated neuropsychiatric through targeting PPIs neurons. interfaces have emerged develop medications less side effects. Dvorak et al. show is an approach psychiatric discovery.

Language: Английский

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Acetylcholine waves and dopamine release in the striatum

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 27, 2023

Abstract Striatal dopamine encodes reward, with recent work showing that release occurs in spatiotemporal waves. However, the mechanism of waves is unknown. Here we report acetylcholine mouse striatum also exhibits wave activity, and spatial scale striatal extended by nicotinic receptors. Based on these findings, our demonstration single cholinergic interneurons can induce release, hypothesized local reciprocal interaction between axons suffices to drive endogenous traveling We show morphological physiological properties interneuron – axon interactions be modeled as a reaction-diffusion system gives rise Analytically-tractable versions model structure nature propagation depend their coupling, give empirically observed correlations signals. Thus, study provides evidence for vivo, proposes testable theoretical framework predicts are strongly coupled phenomena.

Language: Английский

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Comment on 'Accumbens cholinergic interneurons dynamically promote dopamine release and enable motivation'

eLife, Journal Year: 2024, Volume and Issue: 13

Published: May 15, 2024

Acetylcholine is widely believed to modulate the release of dopamine in striatum mammals. Experiments brain slices clearly show that synchronous activation striatal cholinergic interneurons sufficient drive via axo-axonal stimulation nicotinic acetylcholine receptors. However, evidence for this mechanism vivo has been less forthcoming. Mohebi, Collins and Berke recently reported that, awake behaving rats, optogenetic with blue light readily evokes measured red fluorescent sensor RdLight1 (Mohebi et al., 2023). Here, we alone alters properties a manner may be misconstrued as phasic release, artefactual photoactivation can account effects attributed interneurons. Our findings indicate measurements using red-shifted should interpreted caution when combined optogenetics. In other publications did not observe large acetylcholine-evoked transients vivo, conditions under which such occurs animals remain unknown.

Language: Английский

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The nucleus accumbens in reward and aversion processing: insights and implications

Frontiers in Behavioral Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Aug. 9, 2024

The nucleus accumbens (NAc), a central component of the brain's reward circuitry, has been implicated in wide range behaviors and emotional states. Emerging evidence, primarily drawing from recent rodent studies, suggests that function NAc aversion processing is multifaceted. Prolonged stress or drug use induces maladaptive neuronal which results pathological conditions. This review aims to provide comprehensive up-to-date insights on role motivated behavior regulation highlights areas demand further in-depth analysis. It synthesizes latest findings how distinct populations pathways contribute opposite valences. examines neuromodulators, especially monoamines, influence NAc's control over various motivational Furthermore, it delves into complex underlying mechanisms psychiatric disorders such as addiction depression evaluates prospective interventions restore functionality.

Language: Английский

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Generalized cue reactivity in rat dopamine neurons after opioids

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Language: Английский

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Dopamine and acetylcholine correlations in the nucleus accumbens depend on behavioral task states

Current Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Dopamine activity encodes the changing valence of the same stimulus in conditioned taste aversion paradigms

eLife, Journal Year: 2025, Volume and Issue: 13

Published: March 5, 2025

Mesolimbic dopamine encoding of non-contingent rewards and reward-predictive cues has been well established. Considerable debate remains over how mesolimbic responds to aversion in the context aversive conditioning. Inconsistencies may arise from use stimuli that are transduced along different neural paths relative reward or conflation responses avoidance aversion. Here, we made intraoral infusions sucrose measured behavioral varied changing valence sucrose. Pairing with malaise via injection lithium chloride (LiCl) caused development a conditioned taste (CTA), which rendered typically rewarding upon subsequent re-exposure. Following CTA formation, suppressed activity ventral tegmental area neurons (VTA DA ) nucleus accumbens (NAc) release. This pattern signaling after is similar innately quinine contrasts when it was novel not paired LiCl. Dopamine were negatively correlated reactivity predicted home cage preference. Further, scaled strength CTA, increased by repeated LiCl pairings weakened through extinction. Thus, findings demonstrate differential same stimulus according its valence, aligned distinct responses.

Language: Английский

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Local regulation of striatal dopamine: A diversity of circuit mechanisms for a diversity of behavioral functions?

Current Opinion in Neurobiology, Journal Year: 2024, Volume and Issue: 85, P. 102839 - 102839

Published: Feb. 3, 2024

Language: Английский

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