Cognitive Performance during the Development of Diabetes in the Zucker Diabetic Fatty Rat DOI Creative Commons
Marcia Spoelder,

Yami Bright,

Martine C. Morrison

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(20), P. 2463 - 2463

Published: Oct. 16, 2023

Increased insulin levels may support the development of neural circuits involved in cognition, while chronic mild inflammation also result cognitive impairment. This study aimed to gain more insight into whether cognition is already impacted during adolescence a genetic rat model for obesity and type 2 diabetes. Visual discrimination learning throughout level motivation early adulthood were investigated Zucker Diabetic Fatty (ZDF) obese ZDF lean rats using operant touchscreens. Blood glucose, insulin, lipids longitudinally analyzed. Histological analyses performed liver, white adipose tissues, prefrontal cortex. Prior experiments with research model, all experimental assays two groups outbred Long Evans investigate effect different feeding circumstances. Adolescent outperformed on visual performance. During longitudinal testing period, sharply increased over weeks significantly enhanced from 6 age onwards. Early signs liver steatosis enlarged adipocytes tissue observed adult rats. showed no group differences number cortex neurons microglia, nor PSD95 SIRT1 mRNA expression levels. Together, our data show that adolescent even display despite their diabetic profile.

Language: Английский

GABA co-released from striatal dopamine axons dampens phasic dopamine release through autoregulatory GABAA receptors DOI Creative Commons
Jyoti C. Patel,

Ang D. Sherpa,

Riccardo Melani

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(3), P. 113834 - 113834

Published: March 1, 2024

Striatal dopamine axons co-release and gamma-aminobutyric acid (GABA), using GABA provided by uptake via transporter-1 (GAT1). Functions of are poorly understood. We asked whether co-released autoinhibits release axonal type A receptors (GABAARs), complementing established inhibition acting at D2 autoreceptors. show that express α3-GABAAR subunits in mouse striatum. Enhanced evoked single-pulse optical stimulation striatal slices with GABAAR antagonism confirms an endogenous tone limits release. Strikingly, additional inhibitory component is seen when multiple pulses used to mimic phasic activity, revealing the role GABAAR-mediated autoinhibition This autoregulation lost conditional GAT1-knockout mice lacking co-release. Given faster kinetics ionotropic GABAARs than G-protein-coupled autoreceptors, our data reveal a mechanism whereby acts as first responder dampen phasic-to-tonic signaling.

Language: Английский

Citations

15
The nucleus accumbens in reward and aversion processing: insights and implications DOI Creative Commons
Ying Xu, Yingjie Lin, Ming Yu

et al.

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

Citations

8
Local regulation of striatal dopamine: A diversity of circuit mechanisms for a diversity of behavioral functions? DOI
Elizabeth N. Holly, Jamie Galanaugh, Marc V. Fuccillo

et al.

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

Published: Feb. 3, 2024

Language: Английский

Citations

7
Actions and Consequences of Insulin in the Striatum DOI Creative Commons
Jyoti C. Patel, Kenneth D. Carr, Margaret E. Rice

et al.

Biomolecules, Journal Year: 2023, Volume and Issue: 13(3), P. 518 - 518

Published: March 11, 2023

Insulin crosses the blood–brain barrier to enter brain from periphery. In brain, insulin has well-established actions in hypothalamus, as well at level of mesolimbic dopamine neurons midbrain. Notably, also acts striatum, which shows abundant expression receptors (InsRs) throughout. These are found on interneurons and striatal projections neurons, glial cells axons. A striking functional consequence elevation striatum is promoting an increase stimulated release. This boosting release involves InsRs cholinergic interneurons, requires activation nicotinic acetylcholine Opposing this dopamine-enhancing effect, increases uptake through action other well, including projection astrocytes that influence dopaminergic transmission function. Linking these cellular findings behavior, signaling required for development flavor–nutrient learning, implicating a reward signal brain. review, we discuss how they influenced by diet physiological states.

Language: Английский

Citations

13
Cholinergic interneurons in the nucleus accumbens are a site of cellular convergence for corticotropin‐releasing factor and estrogen regulation in male and female mice DOI Creative Commons

Kendra L. Olson,

Anna E. Ingebretson, Eleftheria Vogiatzoglou

et al.

European Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 60(5), P. 4937 - 4953

Published: July 30, 2024

Cholinergic interneurons (ChIs) act as master regulators of striatal output, finely tuning neurotransmission to control motivated behaviours. ChIs are a cellular target many peptide and hormonal neuromodulators, including corticotropin-releasing factor, opioids, insulin leptin, which can influence an animal's behaviour by signalling stress, pleasure, pain nutritional status. However, little is known about how sex hormones via estrogen receptors the function these other neuromodulators. Here, we performed in situ hybridisation on mouse tissue characterise effect choline acetyltransferase (Chat), receptor alpha (Esr1) factor type 1 (Crhr1) expression. Although did not detect differences ChAT protein levels dorsal striatum or nucleus accumbens, found that female mice have more Chat mRNA-expressing neurons than males both accumbens. At population level, observed sexually dimorphic distribution Esr1- Crhr1-expressing ventral was negatively correlated intact females, abolished ovariectomy present males. Only NAc find significant co-express Crhr1 Esr1 females lesser extent transcript were only during estrus phase indicating changes hormone modulate interaction between mRNA levels.

Language: Английский

Citations

5
Extrinsic and intrinsic control of striatal cholinergic interneuron activity DOI Creative Commons

Desh Deepak Ratna,

T. Chase Francis

Frontiers in Molecular Neuroscience, Journal Year: 2025, Volume and Issue: 18

Published: Feb. 13, 2025

The striatum is an integrated component of the basal ganglia responsible for associative learning and response. Besides presence most abundant γ -aminobutyric acid (GABA-ergic) medium spiny neurons (MSNs), also contains distributed populations cholinergic interneurons (ChIs), which bidirectionally communicate with many these neuronal subtypes. Despite their sparse distribution, ChIs provide largest source acetylcholine (ACh) to striatal cells, have a prominent level arborization activity, are potent modulators output play roles in plasticity underlying reinforcement. Deviations from this tonic including phasic bursts or pauses caused by region-selective excitatory input, neuromodulator, neuropeptide release can exert strong influences on intrinsic activity synaptic via diverse receptor signaling. Recent studies new tools allowed improved identification factors driving suppressing peptides. This review aims outline our current understanding that control ChI specifically focusing how neuromodulators neuropeptides interact facilitate suppress responses plasticity.

Language: Английский

Citations

0
Altered leptin signaling and attenuated cardiac vagal activity in rats with type 2 diabetes DOI Creative Commons

Anthony J. Evans,

Huiyin Tu,

Yulong Li

et al.

Frontiers in Physiology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 26, 2025

The leading cause of death in type 2 diabetes mellitus (T2DM) patients is cardiovascular-related events, including myocardial infraction-induced ventricular arrhythmia. Previous studies have shown that T2DM-induced functional remodeling cardiac vagal postganglionic (CVP) neurons contributes to arrhythmogenesis. As leptin resistance common T2DM patients, and CVP are located epicardial adipose pads, a tissue secretes leptin, this study we aimed elucidate correlation between neuronal dysfunction T2DM. A high fat-diet/low dose streptozotocin-induced rat model was used characterize alterations parasympathetic tone, determined by changes baroreflex sensitivity excitability. impact on also studied examining the expression receptors uncoupling protein (UCP2) neurons. rats exhibited diminished sensitivity, decreased excitability, demonstrated reduced frequency action potentials, nAChR currents, an attenuated response nicotine stimulation. Additionally, compared sham animals, UCP2 as early 4 weeks post-T2DM although levels pads increased during progression T2DM, which occurrence Cardiac due, part, develops induction, receptors-UCP2 signaling may contribute dysregulation.

Language: Английский

Citations

0
Leptin as a potential neuroprotective target in Parkinson’s Disease: Exploring its role in Neuroinflammation, oxidative Stress, and dopaminergic neurodegeneration DOI

Vipul Sharma,

Bhat Zada Unjum Saqib,

Khadga Raj Aran

et al.

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Deletion of murine astrocytic vesicular nucleotide transporter increases anxiety and depressive-like behavior and attenuates motivation for reward DOI
Qian Huang,

Hiu Ham Lee,

Bryan Volpe

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 9, 2024

Language: Английский

Citations

2
Recent progress on action and regulation of anorexigenic adipokine leptin DOI Creative Commons
Tadashi Nakagawa,

Toru Hosoi

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: July 20, 2023

Organismal energy balance is controlled by inter-tissue communication mediated the nervous system and hormones, disruption of which causes metabolic syndrome exemplified diabetes obesity. Fat-storing adipose tissue, especially those located in subcutaneous white secretes leptin a proportion fat mass, inhibiting accumulation organismal suppressing appetite promoting expenditure. With prevalence obesity that exhibits hyperleptinemia, most investigation on has been focused how it works does not, expected to be clue for treating In contrast, synthesized, transported, excreted, all are relevant homeostasis blood concentration, not much understood. Of note, acute reduction after hyperleptinemia context exhibited beneficial effect insulin sensitivity, indicating manipulation circulating level may provide therapeutic strategy. Technological advances such as “omics” analysis combined with sophisticated gene-engineered mice studies past decade enabled deeper understanding leptin’s action more detail. Here, we summarize updated well regulation point out emerging direction research leptin.

Language: Английский

Citations

6