Antonia Drinnenberg

All Publications

• How Diverse Retinal Functions Arise from Feedback at the First Visual Synapse. Neuron Drinnenberg, A., Franke, F., Morikawa, R. K., Jüttner, J., Hillier, D., Hantz, P., Hierlemann, A., Azeredo da Silveira, R., Roska, B. 2018

  Abstract

  Many brain regions contain local interneurons of distinct types. How does an interneuron type contribute to the input-output transformations of a given brain region? We addressed this question in the mouse retina by chemogenetically perturbing horizontal cells, an interneuron type providing feedback at the first visual synapse, while monitoring the light-driven spiking activity in thousands of ganglion cells, the retinal output neurons. We uncovered six reversible perturbation-induced effects in the response dynamics and response range of ganglion cells. The effects were enhancing or suppressive, occurred in different response epochs, and depended on the ganglion cell type. A computational model of the retinal circuitry reproduced all perturbation-induced effects and led us to assign specific functions to horizontal cells with respect to different ganglion cell types. Our combined experimental and theoretical work reveals how a single interneuron type can differentially shape the dynamical properties of distinct output channels of a brain region.

  View details for DOI 10.1016/j.neuron.2018.06.001

  View details for PubMedID 29937281

• Congenital Nystagmus Gene FRMD7 Is Necessary for Establishing a Neuronal Circuit Asymmetry for Direction Selectivity NEURON Yonehara, K., Fiscella, M., Drinnenberg, A., Esposti, F., Trenholm, S., Krol, J., Franke, F., Scherf, B., Kusnyerik, A., Mueller, J., Szabo, A., Juettner, J., Cordoba, F., Reddy, A., Nemeth, J., Nagy, Z., Munier, F., Hierlemann, A., Roska, B. 2016; 89 (1): 177–93

  Abstract

  Neuronal circuit asymmetries are important components of brain circuits, but the molecular pathways leading to their establishment remain unknown. Here we found that the mutation of FRMD7, a gene that is defective in human congenital nystagmus, leads to the selective loss of the horizontal optokinetic reflex in mice, as it does in humans. This is accompanied by the selective loss of horizontal direction selectivity in retinal ganglion cells and the transition from asymmetric to symmetric inhibitory input to horizontal direction-selective ganglion cells. In wild-type retinas, we found FRMD7 specifically expressed in starburst amacrine cells, the interneuron type that provides asymmetric inhibition to direction-selective retinal ganglion cells. This work identifies FRMD7 as a key regulator in establishing a neuronal circuit asymmetry, and it suggests the involvement of a specific inhibitory neuron type in the pathophysiology of a neurological disease.

  View details for DOI 10.1016/j.neuron.2015.11.032

  View details for Web of Science ID 000373564300016

  View details for PubMedID 26711119

  View details for PubMedCentralID PMC4712192

• BRAINSTEM NEUROMODULATORY NEURONS PROMOTE GLIOMA GROWTH LOCALLY AND VIA LONG-RANGE PROJECTIONS TO MIDLINE AND CORTICAL STRUCTURES Drexler, R., Drinnenberg, A., Gavish, A., Yalcin, B., Shamardani, K., Rogers, A., Mancusi, R., Taylor, K., Kim, Y., Woo, P., Ravel, A., Tatlock, E., Jokhai, R., Ayala-Sarmiento, A., Rincon-Fernandez, D., Ramakrishnan, C., Siverts, L., Daigle, T., Tasic, B., Zeng, H., Breunig, J., Loh, K., Deisseroth, K., Monje, M. OXFORD UNIV PRESS INC. 2024

  View details for DOI 10.1093/neuonc/noae165.0184

  View details for Web of Science ID 001362572400045

• Cholinergic Neuronal Activity Promotes Diffuse Midline Glioma Growth through Muscarinic Signaling. bioRxiv : the preprint server for biology Drexler, R., Drinnenberg, A., Gavish, A., Yalcin, B., Shamardani, K., Rogers, A., Mancusi, R., Taylor, K. R., Kim, Y. S., Woo, P. J., Ravel, A., Tatlock, E., Ramakrishnan, C., Ayala-Sarmiento, A. E., Pacheco, D. R., Siverts, L., Daigle, T. L., Tasic, B., Zeng, H., Breunig, J. J., Deisseroth, K., Monje, M. 2024

  Abstract

  Neuronal activity promotes the proliferation of healthy oligodendrocyte precursor cells (OPC) and their malignant counterparts, gliomas. Many gliomas arise from and closely resemble oligodendroglial lineage precursors, including diffuse midline glioma (DMG), a cancer affecting midline structures such as the thalamus, brainstem and spinal cord. In DMG, glutamatergic and GABAergic neuronal activity promotes progression through both paracrine signaling and through bona-fide neuron-to-glioma synapses. However, the putative roles of other neuronal subpopulations - especially neuromodulatory neurons located in the brainstem that project to long-range target sites in midline anatomical locations where DMGs arise - remain largely unexplored. Here, we demonstrate that the activity of cholinergic midbrain neurons modulates both healthy OPC and malignant DMG proliferation in a circuit-specific manner at sites of long-range cholinergic projections. Optogenetic stimulation of the cholinergic pedunculopontine nucleus (PPN) promotes glioma growth in pons, while stimulation of the laterodorsal tegmentum nucleus (LDT) facilitates proliferation in thalamus, consistent with the predominant projection patterns of each cholinergic midbrain nucleus. Reciprocal signaling was evident, as increased activity of cholinergic neurons in the PPN and LDT was observed in pontine DMG-bearing mice. In co-culture, hiPSC-derived cholinergic neurons form neuron-to-glioma networks with DMG cells and robustly promote proliferation. Single-cell RNA sequencing analyses revealed prominent expression of the muscarinic receptor genes CHRM1 and CHRM3 in primary patient DMG samples, particularly enriched in the OPC-like tumor subpopulation. Acetylcholine, the neurotransmitter cholinergic neurons release, exerts a direct effect on DMG tumor cells, promoting increased proliferation and invasion through muscarinic receptors. Pharmacological blockade of M1 and M3 acetylcholine receptors abolished the activity-regulated increase in DMG proliferation in cholinergic neuron-glioma co-culture and in vivo. Taken together, these findings demonstrate that midbrain cholinergic neuron long-range projections to midline structures promote activity-dependent DMG growth through M1 and M3 cholinergic receptors, mirroring a parallel proliferative effect on healthy OPCs.

  View details for DOI 10.1101/2024.09.21.614235

  View details for PubMedID 39386427

  View details for PubMedCentralID PMC11463519

• Causal evidence for retina-dependent and -independent visual motion computations in mouse cortex NATURE NEUROSCIENCE Hillier, D., Fiscella, M., Drinnenberg, A., Trenholm, S., Rompani, S. B., Raics, Z., Katona, G., Juettner, J., Hierlemann, A., Rozsa, B., Roska, B. 2017; 20 (7): 960-+

  Abstract

  How neuronal computations in the sensory periphery contribute to computations in the cortex is not well understood. We examined this question in the context of visual-motion processing in the retina and primary visual cortex (V1) of mice. We disrupted retinal direction selectivity, either exclusively along the horizontal axis using FRMD7 mutants or along all directions by ablating starburst amacrine cells, and monitored neuronal activity in layer 2/3 of V1 during stimulation with visual motion. In control mice, we found an over-representation of cortical cells preferring posterior visual motion, the dominant motion direction an animal experiences when it moves forward. In mice with disrupted retinal direction selectivity, the over-representation of posterior-motion-preferring cortical cells disappeared, and their responses at higher stimulus speeds were reduced. This work reveals the existence of two functionally distinct, sensory-periphery-dependent and -independent computations of visual motion in the cortex.

  View details for DOI 10.1038/nn.4566

  View details for Web of Science ID 000404115100012

  View details for PubMedID 28530661

  View details for PubMedCentralID PMC5490790

• Rods in daylight act as relay cells for cone-driven horizontal cell mediated surround inhibition NATURE NEUROSCIENCE Szikra, T., Trenholm, S., Drinnenberg, A., Juettner, J., Raics, Z., Farrow, K., Biel, M., Awatramani, G., Clark, D. A., Sahel, J., da Silveira, R., Roska, B. 2014; 17 (12): 1728–35

  Abstract

  Vertebrate vision relies on two types of photoreceptors, rods and cones, which signal increments in light intensity with graded hyperpolarizations. Rods operate in the lower range of light intensities while cones operate at brighter intensities. The receptive fields of both photoreceptors exhibit antagonistic center-surround organization. Here we show that at bright light levels, mouse rods act as relay cells for cone-driven horizontal cell-mediated surround inhibition. In response to large, bright stimuli that activate their surrounds, rods depolarize. Rod depolarization increases with stimulus size, and its action spectrum matches that of cones. Rod responses at high light levels are abolished in mice with nonfunctional cones and when horizontal cells are reversibly inactivated. Rod depolarization is conveyed to the inner retina via postsynaptic circuit elements, namely the rod bipolar cells. Our results show that the retinal circuitry repurposes rods, when they are not directly sensing light, to relay cone-driven surround inhibition.

  View details for DOI 10.1038/nn.3852

  View details for Web of Science ID 000345484000020

  View details for PubMedID 25344628