Browsing by Author "Meza, Rodrigo"

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    Dendritic Architecture Predicts in vivo Firing Pattern in Mouse Ventral Tegmental Area and Substantia Nigra Dopaminergic Neurons
    (2021) Montero, Trinidad; Gatica, Rafael Ignacio; Farassat, Navid; Meza, Rodrigo; Gonzalez-Cabrera, Cristian; Roeper, Jochen; Henny, Pablo
    The firing activity of ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) dopaminergic (DA) neurons is an important factor in shaping DA release and its role in motivated behavior. Dendrites in DA neurons are the main postsynaptic compartment and, along with cell body and axon initial segment, contribute to action potential generation and firing pattern. In this study, the organization of the dendritic domain in individual VTA and SNc DA neurons of adult male mice, and their relationship to in vivo spontaneous firing, are described. In comparison with dorsal VTA DA neurons, ventrally located VTA neurons (as measured by cell body location) possess a shorter total dendritic length and simpler dendritic architecture, and exhibit the most irregular in vivo firing patterns among DA neurons. In contrast, for DA neurons in the SNc, the higher irregularity of firing was related to a smaller dendritic domain, as measured by convex hull volumes. However, firing properties were also related to the specific regional distribution of the dendritic tree. Thus, VTA DA neurons with a larger extension of their dendritic tree within the parabrachial pigmented (PBP) nucleus fired more regularly compared with those with relatively more dendrites extending outside the PBP. For DA neurons in the SNc, enhanced firing irregularity was associated with a smaller proportion of dendrites penetrating the substantia nigra pars reticulata. These results suggest that differences in dendritic morphology contribute to the in vivo firing properties of individual DA neurons, and that the existence of region-specific synaptic connectivity rules that shape firing diversity.
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    Knockout or Knock-in? A Truncated D2 Receptor Protein Is Expressed in the Brain of Functional D2 Receptor Knockout Mice
    (2021) Sanchez, Natalia; Olivares-Costa, Montserrat; Gonzalez, Marcela P.; Munita, Roberto; Escobar, Angelica P.; Meza, Rodrigo; Herrera-Rojas, Mauricio; Albornoz, Jessica; Merello, Gianluca; Andres, Maria E.
    Null mice for the dopamine D2 receptor (D2R) have been instrumental in understanding the function of this protein. For our research, we obtained the functional D2R knockout mouse strain described initially in 1997. Surprisingly, our biochemical characterization showed that this mouse strain is not a true knockout. We determined by sequence analysis of the rapid 3 ' amplification of cDNA ends that functional D2R knockout mice express transcripts that lack only the eighth exon. Furthermore, immunofluorescence assays showed a D2R-like protein in the brain of functional D2R knockout mice. We verified by immunofluorescence that the recombinant truncated D2R is expressed in HEK293T cells, showing intracellular localization, colocalizing in the Golgi apparatus and the endoplasmic reticulum, but with less presence in the Golgi apparatus compared to the native D2R. As previously reported, functional D2R knockout mice are hypoactive and insensitive to the D2R agonist quinpirole. Concordantly, microdialysis studies confirmed that functional D2R knockout mice have lower extracellular dopamine levels in the striatum than the native mice. In conclusion, functional D2R knockout mice express transcripts that lead to a truncated D2R protein lacking from the sixth transmembrane domain to the C-terminus. We share these findings to avoid future confusion and the community considers this mouse strain in D2R traffic and protein-protein interaction studies.
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    ¿Son efectivos los cannabinoides en la esclerosis múltiple?
    (2017) Meza, Rodrigo; Peña, Javier; García, Karen; Corsi, Oscar; Rada G., Gabriel
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    ¿Son efectivos los corticoides en la necrólisis epidérmica tóxica y el síndrome de Stevens-Johnson?
    (2017) Meza, Rodrigo; Rada G., Gabriel; Varas Arancibia, Pablo Andrés