The choroid plexus synergizes with immune cells during neuroinflammation.

The choroid plexus (ChP) is a vital brain barrier and source of cerebrospinal fluid (CSF). Here, we use longitudinal two-photon imaging in awake mice and single-cell transcriptomics to elucidate the mechanisms of ChP regulation of brain inflammation. We used intracerebroventricular injections of lipopolysaccharides (LPS) to model meningitis in mice and observed that neutrophils and monocytes accumulated in the ChP stroma and surged across the epithelial barrier into the CSF.

Repeated stress triggers seeking of a starvation-like state in anxiety-prone female mice.

Elevated anxiety often precedes anorexia nervosa and persists after weight restoration. Patients with anorexia nervosa often describe self-starvation as pleasant, potentially because food restriction can be anxiolytic. Here, we tested whether repeated stress can cause animals to prefer a starvation-like state.

A spatially-resolved transcriptional atlas of the murine dorsal pons at single-cell resolution.

The "dorsal pons", or "dorsal pontine tegmentum" (dPnTg), is part of the brainstem. It is a complex, densely packed region whose nuclei are involved in regulating many vital functions. Notable among them are the parabrachial nucleus, the Kölliker Fuse, the Barrington nucleus, the locus coeruleus, and the dorsal, laterodorsal, and ventral tegmental nuclei.

Transient cAMP production drives rapid and sustained spiking in brainstem parabrachial neurons to suppress feeding.

Brief stimuli can trigger longer-lasting brain states. G-protein-coupled receptors (GPCRs) could help sustain such states by coupling slow-timescale molecular signals to neuronal excitability. Brainstem parabrachial nucleus glutamatergic (PBN) neurons regulate sustained brain states such as pain and express G-coupled GPCRs that increase cAMP signaling.

Sensitization of meningeal afferents to locomotion-related meningeal deformations in a migraine model.

Migraine headache is hypothesized to involve the activation and sensitization of trigeminal sensory afferents that innervate the cranial meninges. To better understand migraine pathophysiology and improve clinical translation, we used two-photon calcium imaging via a closed cranial window in awake mice to investigate changes in the responses of meningeal afferent fibers using a preclinical model of migraine involving cortical spreading depolarization (CSD). A single CSD episode caused a seconds-long wave of calcium activation that propagated across afferents and along the length of individual afferents.

Cortical reactivations predict future sensory responses.

Many theories of offline memory consolidation posit that the pattern of neurons activated during a salient sensory experience will be faithfully reactivated, thereby stabilizing the pattern. However, sensory-evoked patterns are not stable but, instead, drift across repeated experiences. Here, to investigate the relationship between reactivations and the drift of sensory representations, we imaged the calcium activity of thousands of excitatory neurons in the mouse lateral visual cortex.

A spatially-resolved transcriptional atlas of the murine dorsal pons at single-cell resolution.

The "dorsal pons", or "dorsal pontine tegmentum" (dPnTg), is part of the brainstem. It is a complex, densely packed region whose nuclei are involved in regulating many vital functions. Notable among them are the parabrachial nucleus, the Kölliker Fuse, the Barrington nucleus, the locus coeruleus, and the dorsal, laterodorsal, and ventral tegmental nuclei.

Sensory cortical ensembles exhibit differential coupling to ripples in distinct hippocampal subregions.

Cortical neurons activated during recent experiences often reactivate with dorsal hippocampal CA1 ripples during subsequent rest. Less is known about cortical interactions with intermediate hippocampal CA1, whose connectivity, functions, and ripple events differ from dorsal CA1. We identified three clusters of putative excitatory neurons in mouse visual cortex that are preferentially excited together with either dorsal or intermediate CA1 ripples or suppressed before both ripples.

A collaboration between immune cells and the choroid plexus epithelium in brain inflammation.

The choroid plexus (ChP) is a vital brain barrier and source of cerebrospinal fluid (CSF). Here, we use chronic two-photon imaging in awake mice and single-cell transcriptomics to demonstrate that in addition to these roles, the ChP is a complex immune organ that regulates brain inflammation. In a mouse meningitis model, neutrophils and monocytes accumulated in ChP stroma and surged across the epithelial barrier into the CSF.

Sensitization of meningeal afferents to locomotion-related meningeal deformations in a migraine model.

Migraine headache is hypothesized to involve the activation and sensitization of trigeminal sensory afferents that innervate the cranial meninges. To better understand migraine pathophysiology and improve clinical translation, we used two-photon calcium imaging via a closed cranial window in awake mice to investigate changes in the responses of meningeal afferent fibers using a preclinical model of migraine involving cortical spreading depolarization (CSD). A single CSD episode caused a seconds-long wave of calcium activation that propagated across afferents and along the length of individual afferents.

Competition between stochastic neuropeptide signals calibrates the rate of satiation.

We investigated how transmission of hunger- and satiety-promoting neuropeptides, NPY and αMSH, is integrated at the level of intracellular signaling to control feeding. Receptors for these peptides use the second messenger cAMP. How cAMP integrates opposing peptide signals to regulate energy balance, and the spatiotemporal dynamics of endogenous peptidergic signaling, remain largely unknown.

Neurobiology of eating behavior, nutrition, and health.

Eating behavior and food-related decision making are among the most complex of the motivated behaviors, and understanding the neurobiology of eating behavior, and its developmental dynamics, is critical to advancing the nutritional sciences and public health. Recent advances from both human and animal studies are revealing that individual capacity to make health-promoting food decisions varies based on biological and physiological variation in the signaling pathways that regulate the homeostatic, hedonic, and executive functions; past developmental exposures and current life-stage; the food environment; and complications of chronic disease that reinforce the obese state. Eating rate drives increased calorie intake and represents an important opportunity to lower rates of food consumption and energy intake through product reformulation.

Defining diurnal fluctuations in mouse choroid plexus and CSF at high molecular, spatial, and temporal resolution.

Transmission and secretion of signals via the choroid plexus (ChP) brain barrier can modulate brain states via regulation of cerebrospinal fluid (CSF) composition. Here, we developed a platform to analyze diurnal variations in male mouse ChP and CSF. Ribosome profiling of ChP epithelial cells revealed diurnal translatome differences in metabolic machinery, secreted proteins, and barrier components.

Chronic stress triggers seeking of a starvation-like state in anxiety-prone female mice.

Elevated anxiety often precedes anorexia nervosa and persists after weight restoration. Patients with anorexia nervosa often describe hunger as pleasant, potentially because food restriction can be anxiolytic. Here, we tested whether chronic stress can cause animals to prefer a starvation-like state.

Sensory cortical ensembles exhibit differential coupling to ripples in distinct hippocampal subregions.

Cortical neurons activated during recent experiences often reactivate with dorsal hippocampal CA1 sharp-wave ripples (SWRs) during subsequent rest. Less is known about cortical interactions with intermediate hippocampal CA1, whose connectivity, functions, and SWRs differ from those of dorsal CA1. We identified three clusters of visual cortical excitatory neurons that are excited together with either dorsal or intermediate CA1 SWRs, or suppressed before both SWRs.

Choroid plexus-targeted NKCC1 overexpression to treat post-hemorrhagic hydrocephalus.

Post-hemorrhagic hydrocephalus (PHH) refers to a life-threatening accumulation of cerebrospinal fluid (CSF) that occurs following intraventricular hemorrhage (IVH). An incomplete understanding of this variably progressive condition has hampered the development of new therapies beyond serial neurosurgical interventions. Here, we show a key role for the bidirectional Na-K-Cl cotransporter, NKCC1, in the choroid plexus (ChP) to mitigate PHH.

Transient cAMP production drives rapid and sustained spiking in brainstem parabrachial neurons to suppress feeding.

Brief stimuli can trigger longer lasting brain states. G protein-coupled receptors (GPCRs) could help sustain such states by coupling slow-timescale molecular signals to neuronal excitability. Brainstem parabrachial nucleus glutamatergic neurons (PBN ) regulate sustained brain states such as pain, and express G -coupled GPCRs that increase cAMP signaling.

Brainstem serotonin neurons selectively gate retinal information flow to thalamus.

Retinal ganglion cell (RGC) types relay parallel streams of visual feature information. We hypothesized that neuromodulators might efficiently control which visual information streams reach the cortex by selectively gating transmission from specific RGC axons in the thalamus. Using fiber photometry recordings, we found that optogenetic stimulation of serotonergic axons in primary visual thalamus of awake mice suppressed ongoing and visually evoked calcium activity and glutamate release from RGC boutons.

Trigeminal afferents sense locomotion-related meningeal deformations.

The trigeminal sensory innervation of the cranial meninges is thought to serve a nociceptive function and mediate headache pain. However, the activity of meningeal afferents under natural conditions in awake animals remains unexplored. Here, we used two- and three-dimensional two-photon calcium imaging to track the activity of meningeal afferent fibers in awake mice.

Visual association cortex links cues with conjunctions of reward and locomotor contexts.

Postrhinal cortex (POR) and neighboring lateral visual association areas are necessary for identifying objects and interpreting them in specific contexts, but how POR neurons encode the same object across contexts remains unclear. Here, we imaged excitatory neurons in mouse POR across tens of days prior to and throughout initial cue-reward learning and reversal learning. We assessed responses to the same cue when it was rewarded or unrewarded, during both locomotor and stationary contexts.

History-dependent dopamine release increases cAMP levels in most basal amygdala glutamatergic neurons to control learning.

Dopaminergic inputs to basal amygdala (BA) instruct learning of motivational salience. This learning depends on intracellular plasticity signals such as cyclic adenosine monophosphate (cAMP), which is regulated by activation of dopamine receptors. We examine the dynamics of dopamine release and downstream signaling during multiple salient events occurring within tens of seconds.

Neural basis for regulation of vasopressin secretion by anticipated disturbances in osmolality.

Water balance, tracked by extracellular osmolality, is regulated by feedback and feedforward mechanisms. Feedback regulation is reactive, occurring as deviations in osmolality are . Feedforward or presystemic regulation is proactive, occurring when disturbances in osmolality are .

Cellular activity in insular cortex across seconds to hours: Sensations and predictions of bodily states.

Our wellness relies on continuous interactions between our brain and body: different organs relay their current state to the brain and are regulated, in turn, by descending visceromotor commands from our brain and by actions such as eating, drinking, thermotaxis, and predator escape. Human neuroimaging and theoretical studies suggest a key role for predictive processing by insular cortex in guiding these efforts to maintain bodily homeostasis. Here, we review recent studies recording and manipulating cellular activity in rodent insular cortex at timescales from seconds to hours.