Neural Circuits and Ultrastructure
Lab Director: Maria Medalla, Ph.D.
Tract-tracing, immunohistochemical labeling and multi-channel confocal imaging: Anterograde labeling of two fiber pathways (red and green fibers) combined with immunohistochemical staining of calbindin inhibitory neurons (blue) in monkey prefrontal cortex.
Dr. Medalla’s laboratory investigates the structural and physiological properties of distinct cortical circuits in primate and rodent animal models. Her lab utilizes a combination of cellular in vitro electrophysiological methods with multi-scale anatomical tract-tracing and immunolabeling techniques for light and 3D serial electron microscopy to study the biophysical and synaptic properties of neurons participating in cortical networks important for executive function. The ultimate goal is to understand how these basic cellular and synaptic properties differ across distinct limbic, sensory and motor networks that interact with and are controlled by the prefrontal cortex (PFC), the central executive of the brain.
The major focus of our current projects is on the medial prefrontal anterior cingulate cortex (ACC) in rhesus monkeys –an area important for attention, emotions and context-to-action transformations, and is selectively disrupted in many affective disorders. Specifically, we are studying how the mPFC/ACC interacts with motor-related and limbic memory- and emotion- related cortices and subcortical structures. We are also interested how these prefrontal- motor and limbic networks interface with the cholinergic system, which provides robust neuromodulatory influence over these networks during learning and memory functions.
Recording from identified projection neurons: Projection neurons in ACC directed to PMC were labeled with retrograde FE tracer and identified in acute living slices. Tracer-labeled cells (green) were recorded from and filled with intracellular dye (blue) to label the dendritic arbor.”
3D serial Electron Microscopy: Electron Micrograph and 3D reconstruction of excitatory synapses on spines in lateral prefrontal (LPFC) and primary visual (V1) cortices
Goodliffe JW, Song H, Rubakovic A, Chang W, Medalla M, Weaver CM, Luebke JI. Differential changes to D1 and D2 medium spiny neurons in the 12-month-old Q175+/- mouse model of Huntington’s Disease. PLoS One. 2018 Aug 17;13(8):e0200626. doi: 10.1371/journal.pone.0200626. eCollection 2018.
Guillamon-Vivancos T, Tyler WA, Medalla M, Chang WW, Okamoto M, Haydar TF, Luebke JI. Distinct Neocortical Progenitor Lineages Fine-tune Neuronal Diversity in a Layer-specific Manner. Cereb Cortex. 2018 Feb 03.
Apicco DJ, Ash PEA, Maziuk B, LeBlang C, Medalla M, Al Abdullatif A, Ferragud A, Botelho E, Ballance HI, Dhawan U, Boudeau S, Cruz AL, Kashy D, Wong A, Goldberg LR, Yazdani N, Zhang C, Ung CY, Tripodis Y, Kanaan NM, Ikezu T, Cottone P, Leszyk J, Li H, Luebke J, Bryant CD, Wolozin B. Reducing the RNA binding protein TIA1 protects against tau-mediated neurodegeneration in vivo. Nat Neurosci. 2018 Jan;21(1):72-80. doi: 10.1038/s41593-017-0022-z. Epub 2017 Nov 20.
Medalla M, Gilman JP, Wang JY, Luebke JI. (2017) Strength and Diversity of Inhibitory Signaling Differentiates Primate Anterior Cingulate from Lateral Prefrontal Cortex. J Neurosci. 2017 May 3;37(18):4717-4734. doi: 10.1523/JNEUROSCI.3757-16.2017. Epub 2017 Apr 5. PMID: 28381592
Hilgetag CC, Medalla M, Beul SF, Barbas H. (2016) The Primate Connectome in Context: Principles of Connections of the Cortical Visual System. Neuroimage. 2016 Apr 13. pii: S1053-8119(16)30050-7. Doi: 10.1016/].neuroimage.2016.04.017. [Epub ahead of print]. PMID: 27083526
Gilman JP*, Medalla M*, Luebke JI. (2016) Area-Specific Features of Pyramidal Neurons-a Comparative Study in Mouse and Rhesus Monkey. Cereb Cortex. 2016 Mar 10. pii: bhw062. [Epub ahead of print] PMID: 26965903 *co-first authors
Asai H, Ikezu S, Tsunoda S, Medalla M, Luebke JI, Haydar T, Wolozin B, Butovsky O, Kügler S & Ikezu T (2015), Depletion of microglia and inhibition of exosome synthesis halt tau propagation. Nat Neurosci. 2015 Oct 5. doi: 10.1038/nn.4132. [Epub ahead of print]. PMID: 26436904
Tyler B, Medalla M, Guillamon-Vivancos T, Luebke J and Haydar T. (2015) Distinct iPC lines give rise to different populations of layer 2/3 pyramidal cells in the mouse neocortex. J Neurosci. 2015 Apr 15;35(15):6142-52. doi: 10.1523/JNEUROSCI.0335-15.2015. PMID: 25878286
Medalla M and Luebke, JI. (2015) Diversity of glutamatergic synaptic strength in lateral prefrontal versus primary visual cortices in the rhesus monkey. J Neurosci, 2015 Jan 7; 35(1):112-27. doi: 10.1523/JNEUROSCI.3426-14.2015. PMID: 25568107
For more publications, see Dr. Medalla’s faculty page.