Current Opinion in Neurobiology

Parkinson's disease (PD) is a growing cause of disability worldwide and there is a critical need for the development of disease-modifying therapies to slow or stop disease progression. Recent advances in characterizing the genetics of PD have expanded our understanding of the cell biology of this disorder. Mitochondrial oxidative stress, defects in synaptic function, and impaired lysosomal activity have been shown to be linked in PD, resulting in a pathogenic feedback cycle involving the accumulation of toxic oxidized dopamine and alpha-synuclein...

Astrocytes interact with various cell types, including neurons, vascular cells, microglia, and peripheral immune cells. These interactions are crucial for regulating normal brain functions as well as modulating neuroinflammation in pathological conditions. Recent transcriptomic and proteomic studies have identified critical molecules involved in astrocytic crosstalk with other cells, shedding light on their roles in maintaining brain homeostasis in both healthy and diseased conditions. Astrocytes perform these various roles through either direct or indirect physical associations with neuronal synapses and vasculature...

In the mature brain, functionally distinct areas connect to specific targets, mediating network activity required for function. New insights are still occurring regarding how specific connectivity occurs in the developing brain. Decades of work have revealed important insights into the molecular and genetic mechanisms regulating cell type specification in the brain. This work classified long-range projection neurons of the cerebral cortex into three major classes based on their primary target (e.g. subcortical, intracortical, and interhemispheric projections)...

The entorhinal cortex and hippocampus form a recurrent network that informs many cognitive processes, including memory, planning, navigation, and imagination. Neural recordings from these regions reveal spatially organized population codes corresponding to external environments and abstract spaces. Aligning the former cognitive functionalities with the latter neural phenomena is a central challenge in understanding the entorhinal-hippocampal circuit (EHC). Disparate experiments demonstrate a surprising level of complexity and apparent disorder in the intricate spatiotemporal dynamics of sequential non-local hippocampal reactivations, which occur particularly, though not exclusively, during immobile pauses and rest...

L-DOPA-induced dyskinesia (LID) is the most common form of hyperkinetic movement disorder resulting from altered information processing in the cortico-basal ganglia network. We here review recent advances clarifying the altered interplay between striatal output pathways in this movement disorder. We also review studies revealing structural and synaptic changes to the striatal microcircuitry and altered cortico-striatal activity dynamics in LID. We furthermore highlight the recent progress made in understanding the involvement of cerebellar and brain stem nuclei...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Recently, a confluence between trends in neuroscience and machine learning has brought a renewed focus on unsupervised learning, where sensory processing systems learn to exploit the statistical structure of their inputs in the absence of explicit training targets or rewards. Sophisticated experimental approaches have enabled the investigation of the influence of sensory experience on neural self-organization and its synaptic bases. Meanwhile, novel algorithms for unsupervised and self-supervised learning have become increasingly popular both as inspiration for theories of the brain, particularly for the function of intermediate visual cortical areas, and as building blocks of real-world learning machines...

Chronic stress (CS) can have long-lasting consequences on behavior and cognition, that are associated with stable changes in gene expression in the brain. Recent work has examined the role of the epigenome in the effects of CS on the brain. This review summarizes experimental evidence in rodents showing that CS can alter the epigenome and the expression of epigenetic modifiers in brain cells, and critically assesses their functional effect on genome function. It discusses the influence of the developmental time of stress exposure on the type of epigenetic changes, and proposes new lines of research that can help clarify these changes and their causal involvement in the impact of CS...

Throughout development, the neuronal epigenome is highly sensitive to external stimuli, yet capable of safeguarding cellular memory for a lifetime. In the adult brain, memories of fearful experiences are rapidly instantiated, yet can last for decades, but the mechanisms underlying such longevity remain unknown. Here, we showcase how fear memory formation and storage - traditionally thought to exclusively affect synapse-based events - elicit profound and enduring changes to the chromatin, proposing epigenetic regulation as a plausible molecular template for mnemonic processes...

PTSD is characterized by difficulties in accurately evaluating the threat value of sensory stimuli. While the role of canonical fear and threat neural circuitry in this ability has been well studied, recent lines of evidence suggest a need to include more emphasis on sensory processing in the conceptualization of PTSD symptomology. Specifically, studies have demonstrated a strong association between variability in sensory processing regions and the severity of PTSD symptoms. In this review, we summarize recent findings that underscore the importance of sensory processing in PTSD, in addition to the structural and functional characteristics of associated sensory brain regions...

The descending neurons connecting the fly's brain to its ventral nerve cord respond to sensory stimuli and evoke motor programs of varying complexity. Anatomical characterization of the descending neurons and their synaptic connections suggests how these circuits organize movements, while optogenetic manipulation of their activity reveals what behaviors they can induce. Monitoring their responses to sensory stimuli or during behavior performance indicates what information they may encode. Recent advances in all three approaches make the descending neurons an excellent place to better understand the sensorimotor integration and transformation required for nervous systems to govern the motor sequences that constitute animal behavior...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

The importance of understanding the nonlinear dynamics of neural systems, and the relation to cognitive systems more generally, has been recognised for a long time. Approaches that analyse neural systems in terms of attractors of autonomous networks can be successful in explaining system behaviours in the input-free case. Nonetheless, a computational system usually needs inputs from its environment to effectively solve problems, and this necessitates a non-autonomous framework where typically the effects of a changing environment can be studied...

Connecting neural activity to function is a common aim in neuroscience. How to define and conceptualize function, however, can vary. Here I focus on grounding this goal in the specific question of how a given change in behavior is produced by a change in neural circuits or activity. Artificial neural network models offer a particularly fruitful format for tackling such questions because they use neural mechanisms to perform complex transformations and produce appropriate behavior. Therefore, they can be a means of causally testing the extent to which a neural change can be responsible for an experimentally observed behavioral change...

This review focuses on recent advances made towards understanding the neurobiology of bipolar disorder (BD), a chronic neuropsychiatric illness characterized by altered mood and energy states. The past few years have seen the completion of the largest genetic studies by far, which have emphasized the polygenic nature of BD as well as it's connection to other psychiatric illnesses. Furthermore, the use of inducible pluripotent stem cells has rapidly expanded. These studies support previous work that implicates dysregulation of neurodevelopment, mitochondria, and calcium homeostasis, while also allowing for investigation into the underlying mechanisms of individual responsivity to lithium...

Technical innovation in neuroscience introduced powerful tools for measuring and manipulating neuronal activity via optical, chemogenetic, and calcium-imaging tools. These tools were initially tested primarily in male animals but are now increasingly being used in females as well. In this review, we consider how these tools may work differently in males and females. For example, we review sex differences in the metabolism of chemogenetic ligands and their downstream signaling effects. Optical tools more directly alter depolarization or hyperpolarization of neurons, but biological sex and gonadal hormones modulate synaptic inputs and intrinsic excitability...

N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels widely expressed in the central nervous system that play key role in brain development and plasticity. On the downside, NMDAR dysfunction, be it hyperactivity or hypofunction, is harmful to neuronal function and has emerged as a common theme in various neuropsychiatric disorders including autism spectrum disorders, epilepsy, intellectual disability, and schizophrenia. Not surprisingly, NMDAR signaling is under a complex set of regulatory mechanisms that maintain NMDAR-mediated transmission in check...

Just over a decade ago, a novel GABAergic input originating from a subpopulation of external globus pallidus neurons known as Arkypallidal and projecting exclusively to the striatum was unveiled. At the single-cell level, these pallidostriatal Arkypallidal projections represent one of the largest extrinsic sources of GABA known to innervate the dorsal striatum. This discovery has sparked new questions regarding their role in striatal information processing, the circuit that recruit these neurons, and their influence on behaviour, especially in the context of action selection vs...