Mapping the topographic organization of the human zona incerta using diffusion MRI DOI Creative Commons
Roy A.M. Haast, Jason Kai, Alaa Taha

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 10, 2024

Abstract The zona incerta (ZI) is a deep brain region originally described by Auguste Forel as an “immensely confusing area about which nothing can be said.” Despite the elusive nature of this structure, mounting evidence supports role ZI and surrounding regions across diverse range functions candidate target for neuromodulatory therapies. Using in vivo diffusion MRI data-driven connectivity, we identify topographic organization between neocortex. Specifically, our methods rostral-caudal gradient predominantly connecting frontopolar ventral prefrontal cortices with rostral ZI, primary sensorimotor caudal ZI. Moreover, demonstrate how clustering approaches build complementary including facilitating mapping central connected dorsal cortex. These results were shown to replicable multiple datasets at individual subject level, building important mediating frontal lobe-associated tasks, ranging from motor cognitive emotional control. Finally, consider impact on refinement targets. pave way increasingly detailed understanding substructures, considerations targeting neuromodulation.

Language: Английский

Mapping the topographic organization of the human zona incerta using diffusion MRI DOI Open Access
Roy A.M. Haast, Jason Kai, Alaa Taha

et al.

Published: Feb. 3, 2025

The zona incerta (ZI) is a deep brain region originally described by Auguste Forel as an “immensely confusing area about which nothing can be said.” Despite the elusive nature of this structure, mounting evidence supports role ZI and surrounding regions across diverse range functions candidate target for neuromodulatory therapies. Using in vivo diffusion MRI data-driven connectivity, we identify topographic organization between neocortex. Specifically, our methods rostral-caudal gradient predominantly connecting frontopolar ventral prefrontal cortices with rostral ZI, primary sensorimotor caudal ZI. Moreover, demonstrate how clustering approaches build complementary including facilitating mapping central connected dorsal cortex. These results were shown to replicable multiple datasets at individual subject level, building important mediating frontal lobe-associated tasks, ranging from motor cognitive emotional control. Finally, consider impact on refinement targets. pave way increasingly detailed understanding substructures, considerations targeting neuromodulation.

Language: Английский

Citations

0
Mapping the topographic organization of the human zona incerta using diffusion MRI DOI Open Access
Roy A.M. Haast, Jason Kai, Alaa Taha

et al.

Published: Feb. 3, 2025

The zona incerta (ZI) is a deep brain region originally described by Auguste Forel as an “immensely confusing area about which nothing can be said.” Despite the elusive nature of this structure, mounting evidence supports role ZI and surrounding regions across diverse range functions candidate target for neuromodulatory therapies. Using in vivo diffusion MRI data-driven connectivity, we identify topographic organization between neocortex. Specifically, our methods rostral-caudal gradient predominantly connecting frontopolar ventral prefrontal cortices with rostral ZI, primary sensorimotor caudal ZI. Moreover, demonstrate how clustering approaches build complementary including facilitating mapping central connected dorsal cortex. These results were shown to replicable multiple datasets at individual subject level, building important mediating frontal lobe-associated tasks, ranging from motor cognitive emotional control. Finally, consider impact on refinement targets. pave way increasingly detailed understanding substructures, considerations targeting neuromodulation.

Language: Английский

Citations

0
Zona incerta: from Parkinson's disease to addiction DOI Creative Commons

Marcia A. Wilt,

Robin Magnard, Sébastien Carnicella

et al.

Frontiers in Neural Circuits, Journal Year: 2025, Volume and Issue: 19

Published: Feb. 6, 2025

The zona incerta (ZI), a small and historically overlooked structure located beneath the thalamus, has been increasingly recognized for its role in diverse behavioral processes. Early studies 1970s 1980s explored ingestive behaviors, including drinking feeding (for review, see (Mitrofanis, 2005))(Figure 1a), suggesting involvement motivation survival mechanisms related to food water intake. ZI is now known be heterogeneous nucleus, divided into four major sectors: rostral (ZIr), dorsal (ZId), ventral (ZIv), caudal (ZIc) 2005), each with distinct neurochemical profiles. GABAergic cells, which constitute majority of ZI's neurons, parvalbumin positive neurons are mostly concentrated ZIv, while ZId rich glutamatergic ZIr contains dopaminergic 2005).While motor functions were identified as early 60s (Hyde Toczek, 1962), focus really shifted on those motor-related roles 1990s, became studied context Parkinson's disease (PD) (Shi et al., 2024). introduction deep brain stimulation (DBS) treatment PD patients, subthalamic nucleus (STN) primary target (Benabid 2009), revealed that stimulating nearby also produced significant improvements symptoms (Voges 2002) (Ossowska, 2020). This led renewed interest ZI, placing it spotlight movement disorder therapies. Consequently, non-motor functions, particularly potential reward processes driving behaviors previously characterized, received less attention. However, reports effects following patients-especially mood (Stefurak 2003) , (Tommasi 2008), or emotion (Burrows 2012)-suggested broader ZI. Notably, motivational alterations such apathy (Czernecki, 2005) (Ricciardi 2014) drew attention processes.Today, there link between motivation. contemporary approaches map, monitor manipulate neural circuits improving our understanding contribution different subregions neuronal populations constituting various functions. shares remarkable similarities substantia nigra pars compacta (SNc) tegmental area (VTA), terms their specific involvements behavior (Morales Margolis, 2017). While VTA, more recently SNc, intensively investigated motivation-related pathologies, especially addiction, this aspect remains largely unexamined. Addiction chronic psychiatric defined by loss control over drug intake, despite negative consequences. It involves recurrent periods seeking, withdrawal relapse, leading spiraling addiction cycle (Koob Le Moal, 2008) Volkow, 2010). Recent findings raise new questions about behaviors. short essay examines current evidence disorders akin highlights future research directions.While underexplored, pharmacological support responsiveness drugs abuse. In situ alcohol injection elicits strong responses (Wayner 1975), injections tetrahydropapaveroline, used initiate consumption rats when injected mesocorticolimbic pathway, induces preference (Myers Privette, 1989). Cocaine intake impacts well, increasing Fos expression (Zahm 2010) reducing neurotensin binding, paralleling pathways (Pilotte 1991). Furthermore, morphine tyrosine hydroxylase enhances dopamine (DA) metabolism implicating modulation (Molnar 1994). These indicate abuse directly impact activity, supporting relevance research.The critical features VTA SNc. A first notable parallel 3 structures presence neurons. Dopaminergic transmission from SNc instrumental at core disorders. All trigger DA release striatum, accumbens (NAc) (Di Chiara Imperato, 1988), signaling values valence biologically relevant stimuli (Bromberg-Martin (Schultz, 1998), but encoding prediction errors (RPE) guide learning (Hollerman Schultz, 1998) making mesolimbic nigrostriatal fundamental motivated (Berke, 2018). Alterations these contribute addiction-like excessive seeking taking (Keiflin Janak, 2015) (Goutaudier 2023) (Giuliano 2019) 1997). Very few have focused (ZIDA), recent suggest pivotal (Ye 2023), Specifically, ZIDA overactive during energy deficit, promoting food-seeking maintaining behavior, partly through projections paraventrical thalamus (PVT) 2023). Moreover, seem involved other appetitive self grooming (Jiang Increased observed abstinence, reflecting sociability impairments models (Lalanne 2017) (Homberg stereotypical induced psychostimulants exacerbated drug-sensitization (Kalueff 2016). Excessive marker compulsivity rodent obsessivecompulsive (Mondragón-González consistent connectivity data both human non-human primates highlighted treating obsessive-compulsive (ICDs) (Haber 2023).In addition well-studied contain substantial populations, another feature common Similar (Zhou 2022) (Lowes 2021), (ZIGABA) regulate project NAc (Wang Their optogenetic shown provoke binge-like eating mice, ablation decreases long-term, reduction body weight result (Zhang Van Den Pol, Other types involve ZIGABA, example hunting (Zhao 2019), novelty (Monosov (Ogasawara 2022), trait particular field an endophenotype vulnerability, predicting transition controlled compulsive cocaine use (Belin Deroche-Gamonet, 2012). Optogenetic activation ZIGABA favor exploration objects conspecifics (Ahmadlou 2021). As NAc-projecting undergo activity changes synaptic plasticity exposure (Friend 2021) (Williams 2018), motivation(Ting-A-Kee 2013) (Elum 2024) (Merkel 2024), one can hypothesize neuroadaptations within ZIGABA-NAc circuit may similarly underlie aspects drug-seeking notably disinhibition exploratory toward novel elements environment.Collectively, exposed above highlight point out reinforcement drives phases eventually leads later marked abstinence individuals experience dysphoria, apathy, anxiety, depression pain. likely craving, process whereby sought consumed alleviate affect experienced 1997) (Robbins Beyond motivation, reminiscent state, anxiety (Li pain (Lu implicated aversive connections amygdala thalamic periaqueductal grey (Chou 2018) (Venkataraman Thus, multifaceted posit contributor addiction.Taken together, all withdrawal-related drug-seeking, become evident positioning canonical (Lüscher 2021)(Figure 1b). structural two circuits. bidirectionally connected and, lesser extent, projects NAc, ideally situated modulate midbrain striatum (Arena mentioned above, PVT key player receives inputs prefrontal cortex lateral hypothalamus (Iglesias Flagel, Zhu, 2019). do not provide input 2014), could play modulatory role, linking homeostatic reward-driven processes, modulating indirectly. aligns decrease striatal after electrolytic lesion (Walker Finally, several nuclei cortex, amygdala, habenula (Figure strategically positioned numerous processes.Overall, clear still emerging, addiction-related circuits, pathways, emotion, interoception, theoretical addiction. potentially recapitulating certain extent some VTA/SNc obviously argument underpinning opinion precise discussed, others found no alteration manipulating cell population, limited prehensile (Garau stark contrast place instance. seems widely accepted, distinction GABA must however put perspective, purely co-express neurotransmission markers (Negishi considerations, remain unanswered: Does induce ZI? encode RPE well? Do adaptations drive escalation, symptoms, seeking? Investigating clarify therapeutic relevance. intersection offers intriguing perspectives, only disorders, clinical ICDs, gambling, hypersexuality, eating, prevalent (Houeto 2016) (Leclercq Corvol, resume most psychobiological (Vassileva Conrod, They attributed replacement therapy 2016), pathological underpinnings fully characterized (Prange Thobois, might ZIDA. Interestingly, L-DOPA parkinsonian (Cole 1993) (Bastide hypothesis.ICDs globally well alleviated STN-DBS patients (Scherrer Given anatomical proximity STN suppression ZI-DBS (Mallet 2002), benefit DBS applied neurological (Vorspan (Pelloux Baunez, 2013), considering ICDs (Potenza, emerge avenue addictions. side associated 2020) need investigations delineate sectors optimize strategies.Figure 1: Zona Incerta interest's evolution, function addiction? (A) Evolution topics publications (ZI) 1965 2024. Data obtained bibliometric analysis scientific literature PubMed, articles "zona incerta" title ; primarily tracing, anatomy, cytoarchitecture, neurodevelopment excluded, even if they referenced (n = 213 articles). Bars represent number per decade, main functional thematic categories: (light blue), (medium deep-brain (dark (orange), threat stress-related (green), somatosensory (red), sexual hormones (pink), (yellow), (grey). emphasized started shift 1990s PD, 2010s tremendous increase last years, resurgence (B) Position mediating represented; simplified adapted Luscher 2021. structures, node Amg: Amygdala, DS: Dorsal Striatum, NAc: Nucleus Accumbens, LHb: Lateral Habenula, mPFC: medial Prefrontal Cortex, PVT: ParaVentricular Thalamus, SNc: Substantia Nigra Compacta, vHipp: Hippocampus, VP: Ventral Pallidum, Tegmental Area, ZI: Incerta.

Language: Английский

Citations

0
Restoration of locomotor function following stimulation of the A13 region in Parkinson’s mouse models DOI Open Access
Linda Kim, Adam P. Lognon, Sandeep Sharma

et al.

Published: April 9, 2025

Parkinson’s disease (PD) is characterized by extensive motor and non-motor dysfunction, including gait disturbance, which difficult to treat effectively. This study explores the therapeutic potential of targeting A13 region, a heterogeneous region medial zona incerta (mZI) containing dopaminergic, GABAergic, glutamatergic neurons that has shown relative preservation in PD models. The identified project mesencephalic locomotor (MLR), with subpopulation cells displaying activity correlating movement speed, suggesting its role locomotion. We show photoactivation this can alleviate bradykinesia akinetic features, while increasing turning mouse model PD. These effects combine disease-specific rescue function possible gain function. areas plasticity within mZI connectome using whole-brain imaging. Our findings suggest global remodeling afferent efferent projections highlighting incerta’s as crucial hub for rapid selection unveils significant pro-locomotor suggests promising target PD-related dysfunction.

Language: Английский

Citations

0
Restoration of locomotor function following stimulation of the A13 region in Parkinson’s mouse models DOI Creative Commons
Linda Kim, Adam P. Lognon, Sandeep Sharma

et al.

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

Published: Aug. 6, 2023

ABSTRACT Parkinson’s disease (PD) is characterized by extensive motor and non-motor dysfunction, including gait disturbance, which difficult to treat effectively. This study explores the therapeutic potential of targeting A13 region, a heterogeneous region medial zona incerta (mZI) containing dopaminergic, GABAergic, glutamatergic neurons that has shown relative preservation in PD models. The identified project mesencephalic locomotor (MLR), with subpopulation cells displaying activity correlating movement speed, suggesting its role locomotion. We show photoactivation this can alleviate bradykinesia akinetic features, while increasing turning mouse model PD. These effects combine disease-specific rescue function possible gain function. areas plasticity within mZI connectome using whole-brain imaging. Our findings suggest global remodeling afferent efferent projections highlighting incerta’s as crucial hub for rapid selection unveils significant pro-locomotor suggests promising target PD-related dysfunction. SIGNIFICANCE STATEMENT work examines locomotion, an area direct connectivity regions brainstem. stimulation restore improve model.

Language: Английский

Citations

2
Relaxin family peptide receptor 3 (RXFP3) expressing cells in the zona incerta/lateral hypothalamus augment behavioural arousal DOI Creative Commons
B. Richards, Sarah S. Ch’ng,

Ariel B Simon

et al.

Journal of Neurochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 4, 2024

Abstract Fear‐related psychopathologies, such as post‐traumatic stress disorder, are linked to dysfunction in neural circuits that govern fear memory and arousal. The lateral hypothalamus (LH) zona incerta (ZI) regulate fear, but our understanding of the precise cell types involved remains limited. Here, we examined role relaxin family peptide receptor 3 (RXFP3) expressing cells LH/ZI conditioned expression general arousal male RXFP3‐Cre mice. We found RXFP3+ (LH/ZI RXFP3 ) projected strongly learning, stress, centres, notably, periaqueductal grey, habenula, nucleus reuniens. These do not express hypocretin/orexin or melanin‐concentrating hormone display putative efferent connectivity with LH hypocretin/orexin+ neurons dopaminergic A13 cells. Following Pavlovian conditioning, chemogenetically activating reduced (freezing) overall also induced jumping behaviour increased locomotor activity. Therefore, decreased freezing was more likely reflect enhanced rather than fear. Indeed, stimulating these produced distinct patterns coactivation between several motor, regions, measured by Fos expression. results suggest generates brain‐wide activation augment behavioural image

Language: Английский

Citations

0
Mapping the topographic organization of the human zona incerta using diffusion MRI DOI Creative Commons
Roy A.M. Haast, Jason Kai, Alaa Taha

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 10, 2024

Abstract The zona incerta (ZI) is a deep brain region originally described by Auguste Forel as an “immensely confusing area about which nothing can be said.” Despite the elusive nature of this structure, mounting evidence supports role ZI and surrounding regions across diverse range functions candidate target for neuromodulatory therapies. Using in vivo diffusion MRI data-driven connectivity, we identify topographic organization between neocortex. Specifically, our methods rostral-caudal gradient predominantly connecting frontopolar ventral prefrontal cortices with rostral ZI, primary sensorimotor caudal ZI. Moreover, demonstrate how clustering approaches build complementary including facilitating mapping central connected dorsal cortex. These results were shown to replicable multiple datasets at individual subject level, building important mediating frontal lobe-associated tasks, ranging from motor cognitive emotional control. Finally, consider impact on refinement targets. pave way increasingly detailed understanding substructures, considerations targeting neuromodulation.

Language: Английский

Citations

0