Special Section Guest Editorial: Exploiting Complex Media Photonics to Illuminate Brain's Hidden Depth.

The editorial introduces the Neurophotonics Special Issue "Complex Media NeuroPhotonics," highlighting featured articles.

Advancing the path to imaging in freely moving mice via multimode-multicore fiber based holographic endoscopy.

Significance: Hair-thin multimode optical fiber-based holographic endoscopes have gained considerable interest in modern neuroscience for their ability to achieve cellular and even subcellular resolution during deep brain imaging. However, the application of multimode fibers in freely moving animals presents a persistent challenge as it is difficult to maintain optimal imaging performance while the fiber undergoes deformations.

Aim: We propose a fiber solution for challenging applications with the capability of deep brain high spatial resolution imaging and neuronal activity monitoring in anesthetized as well as awake behaving mice.

Holistic bursting cells store long-term memory in auditory cortex.

The sensory neocortex has been suggested to be a substrate for long-term memory storage, yet which exact single cells could be specific candidates underlying such long-term memory storage remained neither known nor visible for over a century. Here, using a combination of day-by-day two-photon Ca imaging and targeted single-cell loose-patch recording in an auditory associative learning paradigm with composite sounds in male mice, we reveal sparsely distributed neurons in layer 2/3 of auditory cortex emerged step-wise from quiescence into bursting mode, which then invariably expressed holistic information of the learned composite sounds, referred to as holistic bursting (HB) cells. Notably, it was not shuffled populations but the same sparse HB cells that embodied the behavioral relevance of the learned composite sounds, pinpointing HB cells as physiologically-defined single-cell candidates of an engram underlying long-term memory storage in auditory cortex.

Engaging distributed cortical and cerebellar networks through motor execution, observation, and imagery.

When we interact with the environment around us, we are sometimes active participants, making directed physical motor movements and other times only mentally engaging with our environment, taking in sensory information and internally planning our next move without directed physical movement. Traditionally, cortical motor regions and key subcortical structures such as the cerebellum have been tightly linked to motor initiation, coordination, and directed motor behavior. However, recent neuroimaging studies have noted the activation of the cerebellum and wider cortical networks specifically during various forms of motor processing, including the observations of actions and mental rehearsal of movements through motor imagery.

Real-time mechanisms of exacerbated synaptic remodeling by microglia in acute models of systemic inflammation and tauopathy.

Remodeling of synapses by microglia is essential for synaptic plasticity in the brain. However, during neuroinflammation and neurodegenerative diseases, microglia can induce excessive synaptic loss, although the precise underlying mechanisms are unknown. To directly observe microglia-synapse interactions under inflammatory conditions, we performed in vivo two-photon time-lapse imaging of microglia-synapse interactions after bacterial lipopolysaccharide administration to model systemic inflammation, or after inoculation of Alzheimer's disease (AD) brain extracts to model disease-associated neuroinflammatory microglial response.

A corticostriatal projection for sound-evoked and anticipatory motor behavior following temporal expectation.

The ability to form predictions based on recent sensory experience is essential for behavioral adaptation to our ever-changing environment. Predictive encoding represented by neuronal activity has been observed in sensory cortex, but how this neuronal activity is transformed into anticipatory motor behavior remains unclear. Fiber photometry to investigate a corticostriatal projection from the auditory cortex to the posterior striatum during an auditory paradigm in mice, and pharmacological experiments in a task that induces a temporal expectation of upcoming sensory stimuli.

Optical Fiber-Based Recording of Climbing Fiber Ca Signals in Freely Behaving Mice.

The olivocerebellar circuitry is important to convey both motor and non-motor information from the inferior olive (IO) to the cerebellar cortex. Several methods are currently established to observe the dynamics of the olivocerebellar circuitry, largely by recording the complex spike activity of cerebellar Purkinje cells; however, these techniques can be technically challenging to apply in vivo and are not always possible in freely behaving animals. Here, we developed a method for the direct, accessible, and robust recording of climbing fiber (CF) Ca signals based on optical fiber photometry.

Context value updating and multidimensional neuronal encoding in the retrosplenial cortex.

The retrosplenial cortex (RSC) has diverse functional inputs and is engaged by various sensory, spatial, and associative learning tasks. We examine how multiple functional aspects are integrated on the single-cell level in the RSC and how the encoding of task-related parameters changes across learning. Using a visuospatial context discrimination paradigm and two-photon calcium imaging in behaving mice, a large proportion of dysgranular RSC neurons was found to encode multiple task-related dimensions while forming context-value associations across learning.

Visual plasticity: Illuminating the role of the hippocampus in cortical sensory encoding.

The primary visual cortex has the capacity to store stimulus-specific information locally. A new study reveals a direct role for the hippocampus in experience-dependent cortical plasticity when visual stimuli are presented in a predictable temporal order.

A cerebellar-thalamocortical pathway drives behavioral context-dependent movement initiation.

Executing learned motor behaviors often requires the transformation of sensory cues into patterns of motor commands that generate appropriately timed actions. The cerebellum and thalamus are two key areas involved in shaping cortical output and movement, but the contribution of a cerebellar-thalamocortical pathway to voluntary movement initiation remains poorly understood. Here, we investigated how an auditory "go cue" transforms thalamocortical activity patterns and how these changes relate to movement initiation.

Enhanced modulation of cell-type specific neuronal responses in mouse dorsal auditory field during locomotion.

As we move through the environment we experience constantly changing sensory input that must be merged with our ongoing motor behaviors - creating dynamic interactions between our sensory and motor systems. Active behaviors such as locomotion generally increase the sensory-evoked neuronal activity in visual and somatosensory cortices, but evidence suggests that locomotion largely suppresses neuronal responses in the auditory cortex. However, whether this effect is ubiquitous across different anatomical regions of the auditory cortex is largely unknown.

Disynaptic cerebrocerebellar pathways originating from multiple functionally distinct cortical areas.

The cerebral cortex and cerebellum both play important roles in sensorimotor processing, however, precise connections between these major brain structures remain elusive. Using anterograde mono-trans-synaptic tracing, we elucidate cerebrocerebellar pathways originating from primary motor, sensory, and association cortex. We confirm a highly organized topography of corticopontine projections in mice; however, we found no corticopontine projections originating from primary auditory cortex and detail several potential extra-pontine cerebrocerebellar pathways.

High-fidelity multimode fibre-based endoscopy for deep brain in vivo imaging.

Progress in neuroscience relies on new techniques for investigating the complex dynamics of neuronal networks. An ongoing challenge is to achieve minimally invasive and high-resolution observations of neuronal activity in vivo inside deep brain areas. Recently introduced methods for holographic control of light propagation in complex media enable the use of a hair-thin multimode optical fibre as an ultranarrow imaging tool.

The Impact of Visual Cues, Reward, and Motor Feedback on the Representation of Behaviorally Relevant Spatial Locations in Primary Visual Cortex.

The integration of visual stimuli and motor feedback is critical for successful visually guided navigation. These signals have been shown to shape neuronal activity in the primary visual cortex (V1), in an experience-dependent manner. Here, we examined whether visual, reward, and self-motion-related inputs are integrated in order to encode behaviorally relevant locations in V1 neurons.

Optimization of interneuron function by direct coupling of cell migration and axonal targeting.

Neural circuit assembly relies on the precise synchronization of developmental processes, such as cell migration and axon targeting, but the cell-autonomous mechanisms coordinating these events remain largely unknown. Here we found that different classes of interneurons use distinct routes of migration to reach the embryonic cerebral cortex. Somatostatin-expressing interneurons that migrate through the marginal zone develop into Martinotti cells, one of the most distinctive classes of cortical interneurons.

Action and learning shape the activity of neuronal circuits in the visual cortex.

Nonsensory variables strongly influence neuronal activity in the adult mouse primary visual cortex. Neuronal responses to visual stimuli are modulated by behavioural state, such as arousal and motor activity, and are shaped by experience. This dynamic process leads to neural representations in the visual cortex that reflect stimulus familiarity, expectations of reward and object location, and mismatch between self-motion and visual-flow.

Modulation of complex spike activity differs between zebrin-positive and -negative Purkinje cells in the pigeon cerebellum.

The cerebellum is organized into parasagittal zones defined by its climbing and mossy fiber inputs, efferent projections, and Purkinje cell (PC) response properties. Additionally, parasagittal stripes can be visualized with molecular markers, such as heterogeneous expression of the isoenzyme zebrin II (ZII), where sagittal stripes of high ZII expression (ZII+) are interdigitated with stripes of low ZII expression (ZII-). In the pigeon vestibulocerebellum, a ZII+/- stripe pair represents a functional unit, insofar as both ZII+ and ZII- PCs within a stripe pair respond best to the same pattern of optic flow.

Acute in utero exposure to lipopolysaccharide induces inflammation in the pre- and postnatal brain and alters the glial cytoarchitecture in the developing amygdala.

Background: Maternal immune activation (MIA) is a risk factor for neurodevelopmental disorders such as autism and schizophrenia, as well as seizure development. The amygdala is a brain region involved in the regulation of emotions, and amygdalar maldevelopment due to infection-induced MIA may lead to amygdala-related disorders. MIA priming of glial cells during development has been linked to abnormalities seen in later life; however, little is known about its effects on amygdalar biochemical and cytoarchitecture integrity.

A Critical Role for Astrocytes in Hypercapnic Vasodilation in Brain.

Cerebral blood flow (CBF) is controlled by arterial blood pressure, arterial CO, arterial O, and brain activity and is largely constant in the awake state. Although small changes in arterial CO are particularly potent to change CBF (1 mmHg variation in arterial CO changes CBF by 3%-4%), the coupling mechanism is incompletely understood. We tested the hypothesis that astrocytic prostaglandin E (PgE) plays a key role for cerebrovascular CO reactivity, and that preserved synthesis of glutathione is essential for the full development of this response.