Reviews & Analysis

Multiphoton holographic optogenetics is opening the era of ‘tailored’ optogenetics. The authors review the underlying technology and discuss how it can be used to bridge the gap between experimental and theoretical neuroscience.

Schaeffer and Iadecola review the anatomical, molecular and functional heterogeneity of the neurovasculature and highlight the coordinated interaction of factors intrinsic and extrinsic to the brain in its dynamic regulation and role in disease.

Shamash et al. probe the navigational strategies mice use as they escape from a threat. By systematically placing and removing obstacles blocking their initial path, the authors find evidence that mice memorize intermediate ‘subgoal’ locations to find their way home.

Understanding how the brain makes decisions is a major area of focus in both animal and human cognitive neuroscience. Much of this work, especially in primates, has explicated the role of various cortical areas in forming decisions. In new research, perturbations of the superior colliculus by Jun et al. reveal a large and causal role in accumulating evidence for this midbrain structure classically thought of as being involved in simpler functions related to eye movement control.

Ketamine has transformed the treatment of depression by providing rapid relief from depressive symptoms, but the mechanisms mediating its long-term effects are unclear. Kim et al. show that MeCP2 signaling in the hippocampus is critical for supporting sustained antidepressant effects.

Decision-making often involves temporally extended planning and information search. This Review discusses recent theoretical frameworks that have been used to study such naturalistic decision-making and its neural basis.

Sensory information encoding in the mouse brain is more suboptimal when mice make correct decisions than when they make incorrect ones. These suboptimal encoding structures can help information flow between different brain regions, enhancing the ability of these brain regions to work together to make decisions.

Gene replacement therapies have shown remarkable advances recently, including onasemnogene abeparvovec for treatment of symptomatic and presymptomatic patients with spinal muscular atrophy. A recent report by Van Alstyne and colleagues in a mouse model of spinal muscular atrophy raises concerns that such treatment can generate toxic overexpression of SMN protein.

For decades, researchers have wondered whether algorithms used by artificial neural networks might be implemented by biological networks. Payeur et al. have strengthened the connection between neuroscience and artificial intelligence by showing that biologically plausible mechanisms can approximate key features of an essential artificial intelligence learning algorithm.

Hu et al. show that the posterodorsal medial amygdala selectively controls social-reward seeking through its intersection with canonical dopaminergic reward circuits. To identify this circuitry, the authors developed an elegant new affiliative social operant procedure that separates social interaction from social-reward seeking.

In neurodegenerative diseases, certain types of neurons perish first, but the mechanisms of this selective neuronal vulnerability remain unclear. A new study now highlights a crucial role for apolipoprotein E in driving neuronal death in both ageing and Alzheimer’s disease.

Drawing from advances in mathematics and related fields, we show that biophysical models of large-scale neural dynamics can help to bridge the gap between neuromodulation at the cellular scale and mesoscale systems dynamics at the whole-brain level.

Most of the cerebral microcirculation is comprised of capillaries that are lined with pericytes, but the influence of pericytes on local blood flow was not previously established. A new study by Hartmann and colleagues uses selective optical ablation or activation to demonstrate that capillary pericytes exert both static and slow types of regulation on capillary diameter to affect flow, which are distinct from canonical rapid regulation by arteriole smooth muscle.

The act of remembering information or planning actions in short term memory can often be robust to distracting or conflicting information. Finkelstein et al. reveal the neural computations behind this robustness against distractors using a combination of optogenetics, behavior, neural recordings and neural network modelling.

In new research, Smith et al. identify thousands of novel genetic associations with human brain structure and function, including those on the X chromosome, by analyzing ~4,000 MRI-derived traits measured in almost 40,000 individuals from the UK Biobank resource.

Disrupting reconsolidation of the maladaptive memories underlying post-traumatic stress disorder (PTSD) could be transformative for treatment. However, patients cannot undergo the direct re-exposure to trauma-cues used to induce reconsolidation in animal studies. Ressler and colleagues report ‘covert’ memory reactivation in rats, bolstering hopes for translation of reconsolidation-based interventions.

Dong and colleagues investigated mechanisms mediating neurodegeneration in multiple sclerosis and identified a direct role for oxidized phosphatidylcholines (OxPCs) in driving CNS cell death. Microglia activity, mediated by the lipid sensor TREM2 and a neutralizing OxPC antibody, were capable of rescuing OxPC-induced neurotoxicity.

How does the intricate balance of gene regulation and expression within individual neurons relate to electrophysiological oscillations and, ultimately, cognition? In a new study, Berto and colleagues take an important step toward addressing this question by correlating oscillatory biomarkers of successful memory encoding with gene expression on a within-participant basis.

Persistent negative emotional states, such as anxiety, suppress social behavior and vice versa. A new report identifies a novel neural circuit that generates persistent anxiety states and describes how competing excitatory and inhibitory components of this circuit battle to pattern social behavior.

Mandates to include both sexes are a critical step toward improving the translational value of preclinical research, but they will not succeed without intentional, large-scale shifts in scientific incentive structures and publishing standards.