Biology subjects

Udobi, K. C.

Publications and source records attributed to Udobi, K. C..

2 recordsLinked to original sources

bioRxiv2024

Inhibitory basal ganglia nuclei differentially innervate pedunculopontine nucleus subpopulations and evoke opposite motor and valence behaviors.

The canonical basal ganglia model predicts that the substantia nigra pars reticulata (SNr) and the globus pallidus externa (GPe) will have specific effects on locomotion: the SNr inhibiting locomotion and the GPe enhancing it. In this study, we use in vivo optogenetics to show that the GPe exerts non-canonical effects on locomotion while the SNr has no gross motor impact through inhibition of the PPN. We also show that these structures mediate opposing effects on reward. To understand how these structures differentially modulate the PPN, we use ex vivo whole-cell recording with optogenetics to comprehensively dissect the SNr and GPe synaptic connections to regionally- and molecularly-defined populations of PPN neurons. The SNr inhibits all PPN subtypes, but most strongly inhibits caudal glutamatergic neurons. The GPe selectively inhibits caudal glutamatergic and GABAergic neurons, avoiding both cholinergic and rostral cells. This circuit characterization reveals non-canonical basal ganglia pathways for locomotion and valence. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/606694v2_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@11e6a13org.highwire.dtl.DTLVardef@1c63735org.highwire.dtl.DTLVardef@5282b7org.highwire.dtl.DTLVardef@103da4a_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2017

Cognitive deficits and increases in creatine precursors in a brain-specific knockout of the creatine transporter gene Slc6a8

Creatine transporter (CrT; SLC6A8) deficiency (CTD) is an X-linked disorder characterized by severe cognitive deficits, impairments in language, and an absence of brain creatine (Cr). In a previous study, we generated floxed Slc6a8 (Slc6a8flox) mice to create ubiquitous Slc6a8 knockout (Slc6a8-/y) mice. Slc6a8-/y mice lacked whole body Cr and exhibited cognitive deficits. While Slc6a8-/y mice have a similar biochemical phenotype to CTD patients, they also showed a reduction in size and reductions in swim speed that may have contributed to the observed deficits. To address this, we created brain-specific Slc6a8 knockout (bKO) mice by crossing Slc6a8Flox mice with Nestin-cre mice. bKO mice had reduced cerebral Cr levels while maintaining normal Cr levels in peripheral tissue. Interestingly, brain concentrations of the Cr synthesis precursor guanidinoacetic acid were increased in bKO mice. bKO mice had longer latencies and path lengths in the Morris water maze, without reductions in swim speed. In accordance with data from Slc6a8-/y mice, bKO mice showed deficits in novel object recognition as well as contextual and cued fear conditioning. bKO mice were also hyperactive, in contrast with data from the Slc6a8-/y mice. The results demonstrate that the loss of cerebral Cr is responsible for the learning and memory deficits seen in ubiquitous Slc6a8-/y mice.

neuroscience↗