INSIGHT of Medicine(phase 15 ,2024)

1.Optogenetic stimulation of neurons in the anterior cingulate cortex induces changes in intravesical bladder pressure and the micturition reflex

DOI: 10.1038/s41598-024-56806-8

https://www.nature.com/articles/s41598-024-56806-8

Lower urinary tract (LUT) function is controlled by the central nervous system, including higher-order cognitive brain regions. The anterior cingulate cortex (ACC) is one of these regions, but the role of its activity in LUT function remains poorly understood. In the present study, we conducted optogenetic experiments to manipulate neural activity in mouse ACC while monitoring bladder pressure to elucidate how the activity of ACC regulates LUT function. Selective optogenetic stimulation of excitatory neurons in ACC induced a sharp increase in bladder pressure, whereas activation of inhibitory neurons in ACC prolonged the interval between bladder contractions. Pharmacological manipulation of ACC also altered bladder contractions, consistent with those observed in optogenetic experiments. Optogenetic mapping of the cortical area responsible for eliciting the increase in bladder pressure revealed that stimulation to ACC showed more potent effects than the neighboring motor cortical areas. These results suggest that ACC plays a crucial role in initiating the bladder pressure change and the micturition reflex. Thus, the balance between excitation and inhibition in ACC may regulate the reflex bidirectionally.

2.Lateral hypothalamus orexinergic projection to the medial prefrontal cortex modulates chronic stress-induced anhedonia but not anxiety and despair

DOI: 10.1038/s41398-024-02860-9

https://www.nature.com/articles/s41398-024-02860-9

Chronic stress can lead to a combination of anxiety and depression, but the specific neural mechanism behind this is not well understood. In this study, various methods were used to investigate how the lateral hypothalamus (LH) and the medial prefrontal cortex (mPFC) respond to stress and their role in chronic stress-induced anxiety and depression symptoms. The article highlights a new neurocircuitry pathway from LH orexinergic neurons to mPFC and demonstrate its role in regulating anhedonia in response to chronic stress. Under normal circumstances, the LH-mPFC pathway exhibits low activity. However, chronic stress leads to overactivation of LH orexinergic neurons, increasing the release of orexin into the mPFC. This heightened orexin concentration causes increased excitability in the mPFC through specific orexin receptors (OX1R and OX2R), ultimately triggering anhedonia.

3.Local prediction-learning in high-dimensional spaces enables neural networks to plan

DOI: 10.1038/s41467-024-46586-0

https://www.nature.com/articles/s41467-024-46586-0

The process of planning and problem solving in the brain is not well understood. However, this study suggests that learning a cognitive map of the problem space is sufficient for these functions. The researchers found that learning to predict the next observation using local changes in synaptic connections is key to constructing this cognitive map. The cognitive map encodes the relationships between actions and observations, and its high-dimensional geometry provides a sense of direction for reaching distant goals. This quasi-Euclidean sense of direction serves as a simple heuristic for online planning, performing nearly as well as the best offline planning algorithms in artificial intelligence. The article suggests a potential blueprint for energy-efficient neuromorphic hardware capable of acquiring advanced cognitive abilities through autonomous on-chip learning.

4.Local origin of excitatory-inhibitory tuning equivalence in a cortical network

DOI: 10.1038/s41467-024-46586-0

https://www.nature.com/articles/s41593-024-01588-5

The balance between excitation and inhibition in the brain plays a crucial role in determining how information is represented. While the tuning of excitatory neurons is well understood, the principles guiding the tuning of inhibitory neurons remain unclear. This study focused on the mouse postsubiculum (PoSub), where most excitatory neurons encode head-direction (HD). The researchers recorded a population of neurons in the PoSub and found that the tuning of fast-spiking (FS) inhibitory cells, the largest class of cortical inhibitory neurons, was broad and frequently symmetric. Using Fourier transform analysis, they discovered that the tuning of PoSub-FS cells and PoSub-HD cells demonstrated an equivalence in their tuning properties. Understanding the interplay between excitatory and inhibitory neurons and their respective tuning properties provides insight into how cortical representations are formed and maintained.

5.Rhesus infant nervous temperament predicts peri-adolescent central amygdala metabolism & behavioral inhibition measured by a machine-learning approach

DOI: 10.1038/s41398-024-02858-3

https://www.nature.com/articles/s41398-024-02858-3

Anxiety disorders have a profound impact on individuals' well-being and productivity globally. Previous research has shown a connection between early-life behavioral inhibition and the development of these disorders. The central extended amygdala (EAc), including the central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST), has been implicated in anxious and inhibited behavior. Understanding how early-life behavioral inhibition relates to an increased risk of anxiety disorders, mediated by changes in the EAc, could improve treatments and prevention strategies. This study examined the relationship between infant behavioral inhibition, defensive behavior, and brain metabolism in female rhesus monkeys using a behavioral assay and neuroimaging. They found that heightened Ce metabolism predicted increased defensive behavior, while infant nervous temperament was a significant predictor of peri-adolescent defensive behavior. These findings suggest a connection between infant temperament and the future development of anxiety and depressive disorders, highlighting the potential of machine learning tools to enhance behavioral neuroscience research.