Retrograde Tracing with Recombinant Rabies Virus Reveals Correlations Between Projection Targets and Dendritic Architecture in Layer 5 of Mouse Barrel Cortex

A recombinant rabies virus was used as a retrograde tracer to allow complete filling of the axonal and dendritic arbors of identified projection neurons in layer 5 of mouse primary somatosensory cortex (S1) in vivo. Previous studies have distinguished three types of layer 5 pyramids in S1: tall-tufted, tall-simple, and short. Layer 5 pyramidal neurons were retrogradely labeled from several known targets: contralateral S1, superior colliculus, and thalamus. The complete dendritic arbors of labeled cells were reconstructed to allow for unambiguous classification of cell type. We confirmed that the tall-tufted pyramids project to the superior colliculus and thalamus and that short layer 5 pyramidal neurons project to contralateral cortex, as previously described. We found that tall-simple pyramidal neurons contribute to corticocortical connections. Axonal reconstructions show that corticocortical projection neurons have a large superficial axonal arborization locally, while the subcortically projecting neurons limit axonal arbors to the deep layers. Furthermore, reconstructions of local axons suggest that tall-simple cell axons have extensive lateral spread while those of the short pyramids are more columnar. These differences were revealed by the ability to completely label dendritic and axonal arbors in vivo and have not been apparent in previous studies using labeling in brain slices

Dichotomous parvalbumin interneuron populations in dorsolateral and dorsomedial striatum

There are two electrophysiological dichotomous populations of parvalbumin (PV) interneurons located in the dorsal striatum. Striatal PV interneurons in medial and lateral regions differ significantly in their intrinsic excitability. Parvalbumin interneurons in the dorsomedial striatum, but not in the dorsolateral striatum, receive afferent glutamatergic input from cingulate cortex.Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard and a doctoral fellowship from the Portuguese Foundation for Science and Technology to P.M. (SFRH/BD/33894/2009). Research in the Laboratory of Guoping Feng has been supported by the Poitras Center for Affective Disorders Research at MIT, Stanley Center for Psychiatric Research at Broad Institute of MIT and Harvard, National Institute of Health (NINDS and NIMH), Alfred P. Sloan Foundation, American Heart Association, The Arnold and Mabel Beckman Foundation, The EJLB Foundation, The Esther A. & Joseph Klingenstein Fund, The Hartwell Foundation, March of Dimes Birth Defects Foundation, McKnight Endowment Fund for Neuroscience, Nancy Lurie Marks Family Foundation, Ruth K. Broad Foundation for Biomedical Research, Simons Foundation Autism Research Initiative (SFARI), and The Whitehall Foundation. B.B. was supported by postdoctoral fellowships from the Simons Center for the Social Brain at MIT and the Autism Science Foundation and is currently a faculty at The School of Psychological Sciences and Sagol School of Neuroscience, Tel Aviv University, Israel. P.M. is currently supported by Society in Science, The Branco Weiss Fellowship, administered by Eidgenössische Technische Hochschule (ETH) Zürich, and European Molecular Biology Organization (EMBO) Long-Term Fellowship (ALTF 89 – 2016)info:eu-repo/semantics/publishedVersio

Compensatory remodeling of a septo-hippocampal GABAergic network in the triple transgenic Alzheimer’s mouse model

Abstract Background Alzheimer’s disease (AD) is characterized by a progressive loss of memory that cannot be efficiently managed by currently available AD therapeutics. So far, most treatments for AD that have the potential to improve memory target neural circuits to protect their integrity. However, the vulnerable neural circuits and their dynamic remodeling during AD progression remain largely undefined. Methods Circuit-based approaches, including anterograde and retrograde tracing, slice electrophysiology, and fiber photometry, were used to investigate the dynamic structural and functional remodeling of a GABAergic circuit projected from the medial septum (MS) to the dentate gyrus (DG) in 3xTg-AD mice during AD progression. Results We identified a long-distance GABAergic circuit that couples highly connected MS and DG GABAergic neurons during spatial memory encoding. Furthermore, we found hyperactivity of DG interneurons during early AD, which persisted into late AD stages. Interestingly, MS GABAergic projections developed a series of adaptive strategies to combat DG interneuron hyperactivity. During early-stage AD, MS-DG GABAergic projections exhibit increased inhibitory synaptic strength onto DG interneurons to inhibit their activities. During late-stage AD, MS-DG GABAergic projections form higher anatomical connectivity with DG interneurons and exhibit aberrant outgrowth to increase the inhibition onto DG interneurons. Conclusion We report the structural and functional remodeling of the MS-DG GABAergic circuit during disease progression in 3xTg-AD mice. Dynamic MS-DG GABAergic circuit remodeling represents a compensatory mechanism to combat DG interneuron hyperactivity induced by reduced GABA transmission

Transsynaptic tracing by in situ complementation of a deletion mutant neurotropic virus

We have developed two new tools for tracing neural connections. The first is a means of identifying cells that project to a region of interest within the brain, illuminating these cells with intense fluorescence and allowing their finest morphological details to be seen. This permits either highly detailed reconstruction of the cells' anatomy or their targeting, in live tissue, on the basis of their morphology for physiological study. The second tool is a means of identifying, on a large scale, neurons which are directly presynaptic to either a targeted cell type or indeed a single neuron. Because this technique also results in intensely fluorescent cellular details, this too could be used either for detailed anatomical studies or for physiological ones. This should allow a significantly more precise understanding of the organization of nervous systems than has previously been possibl