Biology subjects

Brandenburg, C.

Publications and source records attributed to Brandenburg, C..

6 recordsLinked to original sources

bioRxiv2026

Frequency-dependent cerebellar circuits independently gate social vocalizations and movement

Communication depends on precise coordination between motor execution and cognition. Here we reveal that the cerebellum exerts real-time control over social vocalizations in adult mice. Optogenetic activation of excitatory cerebellar output in the superior cerebellar peduncle suppressed ultrasonic vocalizations with frequency-dependent potency while inducing distinct motor phenotypes. Systematic, functional mapping across cerebellar regions and cell types revealed that vocal suppression can occur in the absence of overt motor impairment, suggesting selective control of vocal output beyond gross movement disruption. We identified the periaqueductal gray (PAG), a conserved midbrain vocal control center, as a key downstream mediator of this effect. Deep brain stimulation of the PAG rescued vocal deficits in a model of cerebellar dysfunction without rescuing motor incoordination. These findings define a cerebellar-midbrain pathway that gates vocal behavior and demonstrate that targeted therapeutic neuromodulation can selectively restore communication-related output even in the presence of persistent cerebellar-driven motor deficits.

neuroscience↗

bioRxiv2025

Cerebellar Purkinje cell stripe patterns reveal a differential vulnerability and resistance to cell loss during normal aging in mice

Age-related neurodegenerative diseases involve reduced cell numbers and impaired behavioral capacity. Neurodegeneration and behavioral deficits also occur during aging, and notably in the absence of disease. The cerebellum, which modulates movement and cognition, is susceptible to cell loss in both aging and disease. Here, we demonstrate that cerebellar Purkinje cell loss in aged mice is not spatially random but rather occurs in a pattern of parasagittal stripes. We also find that aged mice exhibit impaired motor coordination and more severe tremor compared to younger mice. However, the relationship between patterned Purkinje cell loss and motor dysfunction is not straightforward. Examination of postmortem samples of human cerebella from neurologically typical individuals supports the presence of selective loss of Purkinje cells during aging. These data reveal a spatiotemporal cellular substrate for aging in the cerebellum that may inform how neuronal vulnerability leads to neurodegeneration and the ensuing deterioration of behavior.

neuroscience↗

bioRxiv2024

Developmental transformations of Purkinje cells tracked by DNA electrokinetic mobility

Brain development relies on orchestrated placement and timing of neurogenesis in progenitor zones to produce the expansive cellular diversity of the brain. We took advantage of bioelectric interactions between DNA and embryonic tissue to perform "stereo-tracking", a developmental targeting strategy that differentially labels cells positioned at different depths within intact progenitor zones. This three-dimensional labeling was achieved by delivery of plasmids with distinct electrokinetic mobilities into neural progenitor zones in utero. We applied stereo-tracking with light sheet imaging in the cerebellum and identified that Purkinje cells follow embryonically committed developmental trajectories linking distinct progenitor zone fields to the topography of the mature cerebellar cortex. In the process of stereo-tracking, we identified a previously unreported subcellular structure on the axon initial segment of Purkinje cells. These structures, we termed "axon bubbles", are developmentally timed and differentially labeled by lipid-modified proteins. Our findings demonstrate key rules that orchestrate the stereotyped transformations from fetal progenitors into mature networks of neuronal circuits, and demonstrate the potential of progenitor zone stereo-tracking to reveal new biology within intact developing systems.

neuroscience↗

bioRxiv2024

Symmetry in levels of axon-axon homophilic adhesion establishes topography in the corpus callosum and development of connectivity between brain hemispheres

Specific and highly diverse connectivity between functionally specialized regions of the nervous system is controlled at multiple scales, from anatomically organized connectivity following macroscopic axon tracts to individual axon target-finding and synapse formation. Identifying mechanisms that enable entire subpopulations of related neurons to project their axons with regional specificity within stereotyped tracts to form appropriate long-range connectivity is key to understanding brain development, organization, and function. Here, we investigate how axons of the cerebral cortex form precise connections between the two cortical hemispheres via the corpus callosum. We identify topographic principles of the developing trans-hemispheric callosal tract that emerge through intrinsic guidance executed by growing axons in the corpus callosum within the first postnatal week in mice. Using micro-transplantation of regionally distinct neurons, subtype-specific growth cone purification, subcellular proteomics, and in utero gene manipulation, we investigate guidance mechanisms of transhemispheric axons. We find that adhesion molecule levels instruct tract topography and target field guidance. We propose a model in which transcallosal axons in the developing brain perform a "handshake" that is guided through co-fasciculation with symmetric contralateral axons, resulting in the stereotyped homotopic connectivity between the brains hemispheres.

neuroscience↗

bioRxiv2022

Region-specific alterations of perineuronal net expression in postmortem autism brain tissue

Genetic variance in ASD is often associated with mechanisms that broadly fall into the category of neuroplasticity. Parvalbumin positive neurons and their surrounding perineuronal nets (PNNs) are important factors in critical period plasticity and have both been implicated in ASD. PNNs are found in high density within output structures of the cerebellum and basal ganglia, two regions that are densely connected to many other brain areas and have the potential to participate in the diverse array of symptoms present in an ASD diagnosis. The dentate nucleus and globus pallidus were therefore assessed for differences in PNN expression in human postmortem ASD brain tissue. While Purkinje cell loss is a consistent neuropathological finding in ASD, in this cohort, the Purkinje cell targets within the dentate nucleus did not show differences in number of cells with or without a PNN. However, the density of parvalbumin positive neurons with a PNN were significantly reduced in the globus pallidus internus and externus of ASD cases, which was not dependent on seizure status. It is unclear whether these alterations manifest during development or are a consequence of activity-dependent mechanisms that lead to altered network dynamics later in life.

neuroscience↗

bioRxiv2021

Differential chemoarchitecture of Purkinje neurons contributes to intrinsic firing properties

Purkinje cells (PCs) are central to cerebellar information coding and appreciation for the diversity of their firing patterns and molecular profiles is growing. Heterogeneous subpopulations of PCs have been identified that display differences in intrinsic firing properties without clear mechanistic insight into what underlies the divergence in firing parameters. Although long used as a general PC marker, we report that the calcium binding protein parvalbumin labels a subpopulation of PCs with a conserved distribution pattern across the animals examined. We trained a convolutional neural network to recognize the parvalbumin-positive subtype and create maps of whole cerebellar distribution and find that PCs within these areas have differences in spontaneous firing that can be modified by altering calcium buffer content. These subtypes also show differential responses to potassium and calcium channel blockade, suggesting a mechanistic role for variability in PC intrinsic firing through differences in ion channel composition. It is proposed that ion channels drive the diversity in PC intrinsic firing phenotype and parvalbumin calcium buffering provides capacity for the highest firing rates observed. These findings open new avenues for detailed classification of PC subtypes.

neuroscience↗