Volume 25 Issue 5, May 2022

Two recent papers reveal that the brain can regulate its own immune responses by sending molecular cues to immune cells in the skull bone marrow via the cerebrospinal fluid. Furthermore, experimental spinal cord injury or bacterial meningitis specifically activate local vertebral and skull-resident hematopoietic cell injury responses.

Pettit, Yuan and Harvey find that hippocampal spatial maps degrade when mice voluntarily disengage from a navigation task, even without changes in sensory or self-motion cues. This finding suggests that internal state could have an active role in supporting navigational coding and, perhaps, spatial memory.

Degeneration of dopaminergic neurons in the substantia nigra is a pathological hallmark of Parkinson’s disease (PD). However, not all dopamine-producing neurons degenerate. Kamath, Abdulraouf et al. find that there are ten transcriptionally defined dopaminergic subpopulations in the human substantia nigra, but only one carries significant PD genetic risk and is vulnerable to neurodegeneration in PD.

Activity-regulated myelination adaptively tunes neural circuit function in health. In rodent models of generalized epilepsy, recurrent seizures aberrantly increase myelination specifically within the seizure circuit. Blocking this seizure-induced myelination abrogates the progressive increase in seizure burden and ictal hypersynchrony that occurs in mice with intact activity-regulated myelination, indicating that maladaptive myelination can contribute to disease progression in epilepsy.

Dopamine (DA) neurons in the ventral tegmental area bidirectionally regulate the activity of serotonin neurons in the dorsal raphe nucleus. Low-strength activity causes inhibition via dopamine receptor D2, whereas high- strength activity causes activation via dopamine receptor D1, and this circuit contributes to anorexia nervosa-like behaviors in mice.

Eating disorders are prevalent and, in far too many cases, fatal. This review covers advances in genetics, neuroimaging, and animal models, and encourages a more unified science of eating disorders.

Mazzitelli, Smyth and colleagues show that cerebrospinal fluid gains direct access to skull bone marrow niches via dura–skull channels, allowing for the CNS context-dependent regulation of immune supply to the meninges.

The authors found that the expression of spatial maps in the hippocampus is modulated by the internal state of an animal. Thus, the brain’s code for spatial positions within an environment can transform even without changes to the external world.

This manuscript describes a new cerebral spinal fluid exit route via hundreds of skull channels, with the cranial bone marrow as a destination. In meningitis, bacteria hijack this path and alert hematopoietic stem cells residing in the skull marrow.

This study finds that during acute viral infection of the CNS, meningeal lymphatic vessels (MLVs) can transport virus from the CNS to draining cervical lymph nodes. VEGF-C-induced expansion of functional MLVs facilitated virus clearance.

The authors used single-cell genomics to profile thousands of human dopamine neurons and identify one uniquely Parkinson’s disease-susceptible population, which was enriched for genetic risk for Parkinson’s disease.

Recurrent absence seizures aberrantly increase activity-regulated myelination within the seizure network; this maladaptive myelination, in turn, increases network hypersynchrony and seizure burden over time.

Using voltage imaging, Armbruster et al. show that neuronal activity induces large, rapid and synapse-specific astrocyte depolarizations that enhance synaptic glutamate signaling, representing a novel form of neuron–astrocyte communication.

Bertels et al. identify that spinal neurons switch neurotransmitter phenotype from excitation to inhibition after spinal cord injury. Manipulation of neurotransmitter phenotype reveals that maintaining excitatory phenotype is essential for locomotor recovery.

Li et al. report a key brain region in the hypothalamus that effectively modulates the production and properties of new neurons generated in adulthood. These hypothalamic modified new neurons are critical for memory and anxiety-like behavior.

The authors show that stimulus strength-dependent effects of DA on 5-HT^DRN neurons bidirectionally regulate feeding in mice. DRD1-mediated activation of 5-HT^DRN neurons contributes to activity-based anorexia, and this can be prevented by blocking DRD1.

The authors present a circuit tracing method, Trans-Seq, which determines the targets of a given neuron type through anterograde tracing combined with single-cell RNA sequencing. Applying Trans-Seq to retinotectal synapses, the authors find a selective connection assembled by Nephronectin.