Medium spiny neurons activity reveals the discrete segregation of mouse dorsal striatum
Abstract
Behavioural studies differentiate the rodent dorsal striatum (DS) into lateral and medial regions; however, anatomical evidence suggests that it is a unified structure. To understand striatal dynamics and basal ganglia functions, it is essential to clarify the circuitry that supports this behavioural-based segregation. Here, we show that the mouse DS is made of two non-overlapping functional circuits divided by a boundary. Combining in vivo optopatch-clamp and extracellular recordings of spontaneous and evoked sensory activity, we demonstrate different coupling of lateral and medial striatum to the cortex together with an independent integration of the spontaneous activity, due to particular corticostriatal connectivity and local attributes of each region. Additionally, we show differences in slow and fast oscillations and in the electrophysiological properties between striatonigral and striatopallidal neurons. In summary, these results demonstrate that the rodent DS is segregated in two neuronal circuits, in homology with the caudate and putamen nuclei of primates.
Data availability
All data generated during and/or analysed during the current study, as well as the required code to reproduce the figures, is available on the CSIC public repository. This is the URL access http://dx.doi.org/10.20350/digitalCSIC/13750.
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Medium spiny neurons activity reveals the discrete segregation of mouse dorsal striatumCSIC, 10.20350/digitalCSIC/13750.
Article and author information
Author details
Funding
Ministerio de Economía, Industria y Competitividad, Gobierno de España (BFU2014-60809-IN)
- Ramon Reig
Ministerio de Economía, Industria y Competitividad, Gobierno de España (SEV-2013-0317 and SEV-2017-0723)
- Ramon Reig
Ministerio de Economía, Industria y Competitividad, Gobierno de España (SEV2013-0317)
- María Sáez
Fundacion la Caixa (2016/00006/001)
- Roberto Montanari
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All the experimental procedures were conformed to the directive 2010/63/EU of the European Parliament and the RD 53/2013 Spanish regulation on the protection of animals use for scientific purposes, approved by the government of the Autonomous Community of Valencia, under the supervision of the Consejo Superior de Investigaciones Científicas and the Miguel Hernandez University Committee for Animal use in Laboratory.
Copyright
© 2021, Alegre-Cortés et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Further reading
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- Neuroscience
Sleep cycles are defined as episodes of non-rapid eye movement (non-REM) sleep followed by an episode of REM sleep. Fractal or aperiodic neural activity is a well-established marker of arousal and sleep stages measured using electroencephalography. We introduce a new concept of ‘fractal cycles’ of sleep, defined as a time interval during which time series of fractal activity descend to their local minimum and ascend to the next local maximum. We assess correlations between fractal and classical (i.e. non-REM – REM) sleep cycle durations and study cycles with skipped REM sleep. The sample comprised 205 healthy adults, 21 children and adolescents and 111 patients with depression. We found that fractal and classical cycle durations (89±34 vs 90±25 min) correlated positively (r=0.5, p<0.001). Children and adolescents had shorter fractal cycles than young adults (76±34 vs 94±32 min). The fractal cycle algorithm detected cycles with skipped REM sleep in 91–98% of cases. Medicated patients with depression showed longer fractal cycles compared to their unmedicated state (107±51 vs 92±38 min) and age-matched controls (104±49 vs 88±31 min). In conclusion, fractal cycles are an objective, quantifiable, continuous and biologically plausible way to display sleep neural activity and its cycles.
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- Medicine
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Background:
Subarachnoid hemorrhage (SAH) is characterized by intense central inflammation, leading to substantial post-hemorrhagic complications such as vasospasm and delayed cerebral ischemia. Given the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation (taVNS) and its ability to promote brain plasticity, taVNS has emerged as a promising therapeutic option for SAH patients. However, the effects of taVNS on cardiovascular dynamics in critically ill patients, like those with SAH, have not yet been investigated. Given the association between cardiac complications and elevated risk of poor clinical outcomes after SAH, it is essential to characterize the cardiovascular effects of taVNS to ensure this approach is safe in this fragile population. Therefore, this study assessed the impact of both acute and repetitive taVNS on cardiovascular function.
Methods:
In this randomized clinical trial, 24 SAH patients were assigned to either a taVNS treatment or a sham treatment group. During their stay in the intensive care unit, we monitored patient electrocardiogram readings and vital signs. We compared long-term changes in heart rate, heart rate variability (HRV), QT interval, and blood pressure between the two groups. Additionally, we assessed the effects of acute taVNS by comparing cardiovascular metrics before, during, and after the intervention. We also explored acute cardiovascular biomarkers in patients exhibiting clinical improvement.
Results:
We found that repetitive taVNS did not significantly alter heart rate, QT interval, blood pressure, or intracranial pressure (ICP). However, repetitive taVNS increased overall HRV and parasympathetic activity compared to the sham treatment. The increase in parasympathetic activity was most pronounced from 2 to 4 days after initial treatment (Cohen’s d = 0.50). Acutely, taVNS increased heart rate, blood pressure, and peripheral perfusion index without affecting the corrected QT interval, ICP, or HRV. The acute post-treatment elevation in heart rate was more pronounced in patients who experienced a decrease of more than one point in their modified Rankin Score at the time of discharge.
Conclusions:
Our study found that taVNS treatment did not induce adverse cardiovascular effects, such as bradycardia or QT prolongation, supporting its development as a safe immunomodulatory treatment approach for SAH patients. The observed acute increase in heart rate after taVNS treatment may serve as a biomarker for SAH patients who could derive greater benefit from this treatment.
Funding:
The American Association of Neurological Surgeons (ALH), The Aneurysm and AVM Foundation (ALH), The National Institutes of Health R01-EB026439, P41-EB018783, U24-NS109103, R21-NS128307 (ECL, PB), McDonnell Center for Systems Neuroscience (ECL, PB), and Fondazione Neurone (PB).
Clinical trial number: