Person:
Oldenburg, Ian Anton

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Oldenburg

First Name

Ian Anton

Name

Oldenburg, Ian Anton
Author's Publications: search.filters.isAuthorOfPublication.83740928-0c29-4752-8d05-4fe238f73bc2

Search Results

Now showing 1 - 3 of 3
  • Thumbnail Image
    Publication
    Basal Ganglia Modulation of Cortical Firing Rates in a Behaving Animal
    (2014-10-22) Oldenburg, Ian Anton; Sabatini, Bernardo Luis; Wilson, Rachel; Andermann, Mark; Harvey, Christopher; Moore, Chris
    Motor cortex, basal ganglia (BG), and thalamus are anatomically arranged in a recurrent loop whose activity is hypothesized to be involved in the selection of motor actions. Direct (dSPN) and indirect (iSPN) striatal projection neurons receive excitatory input from cortex, and are thought to oppositely modulate cortical activity via BG output to thalamus. Here, we test the central tenets of this model in head-restrained mice performing an operant conditioning task using optogenetic manipulation of dSPNs and iSPNs to determine the effects of activity in each pathway on primary motor cortex. We find that dSPN and iSPN activation has bidirectional, robust, and rapid effects on motor cortex that are highly context-dependent, with distinct effects of each pathway during quiescent and active periods. Thus, the effects of activity in each pathway are at times antagonistic and consistent with classic models, whereas in other behavioral contexts the two pathways will work in the same direction or have no effect at all. In a separate but related project, we describe a direct projection from the globus pallidus externa (GP), a central nucleus of the BG, to frontal regions of the cerebral cortex (FC), which is not typically included in models of BG function. Two cell types make up the GP-FC projection, distinguished by their electrophysiological properties, cortical projection patterns and expression of choline acyteltransferase (ChAT), a genetic marker for the neurotransmitter acetylcholine. These cholinergic GP cells receive basal ganglia input and bidirectionally modulate firing in FC of awake mice. Since GP-FC cells receive dopamine sensitive inhibition from iSPNs and dSPNs, this circuit reveals a pathway by which neuropsychiatric pharmaceuticals can act in the BG and yet modulate frontal cortices. Together, these two projects expand our understanding of the complexities of basal ganglia circuitry and its interactions with cortex.
  • Thumbnail Image
    Publication
    Vesicular Stomatitis Virus with the Rabies Virus Glycoprotein Directs Retrograde Transsynaptic Transport Among Neurons In Vivo
    (Frontiers Media S.A., 2013) Beier, Kevin Thomas; Saunders, Arpiar; Oldenburg, Ian Anton; Sabatini, Bernardo; Cepko, Constance
    Defining the connections among neurons is critical to our understanding of the structure and function of the nervous system. Recombinant viruses engineered to transmit across synapses provide a powerful approach for the dissection of neuronal circuitry in vivo. We recently demonstrated that recombinant vesicular stomatitis virus (VSV) can be endowed with anterograde or retrograde transsynaptic tracing ability by providing the virus with different glycoproteins. Here we extend the characterization of the transmission and gene expression of recombinant VSV (rVSV) with the rabies virus glycoprotein (RABV-G), and provide examples of its activity relative to the anterograde transsynaptic tracer form of rVSV. rVSV with RABV-G was found to drive strong expression of transgenes and to spread rapidly from neuron to neuron in only a retrograde manner. Depending upon how the RABV-G was delivered, VSV served as a polysynaptic or monosynaptic tracer, or was able to define projections through axonal uptake and retrograde transport. In animals co-infected with rVSV in its anterograde form, rVSV with RABV-G could be used to begin to characterize the similarities and differences in connections to different areas. rVSV with RABV-G provides a flexible, rapid, and versatile tracing tool that complements the previously described VSV-based anterograde transsynaptic tracer.
  • Thumbnail Image
    Publication
    Cholinergic Interneurons Mediate Fast VGluT3-Dependent Glutamatergic Transmission in the Striatum
    (Public Library of Science, 2011) Higley, Michael J.; Gittis, Aryn H.; Oldenburg, Ian Anton; Balthasar, Nina; Seal, Rebecca P.; Edwards, Robert H.; Lowell, Bradford; Kreitzer, Anatol C.; Sabatini, Bernardo
    The neurotransmitter glutamate is released by excitatory projection neurons throughout the brain. However, non-glutamatergic cells, including cholinergic and monoaminergic neurons, express markers that suggest that they are also capable of vesicular glutamate release. Striatal cholinergic interneurons (CINs) express the Type-3 vesicular glutamate transporter (VGluT3), although whether they form functional glutamatergic synapses is unclear. To examine this possibility, we utilized mice expressing Cre-recombinase under control of the endogenous choline acetyltransferase locus and conditionally expressed light-activated Channelrhodopsin2 in CINs. Optical stimulation evoked action potentials in CINs and produced postsynaptic responses in medium spiny neurons that were blocked by glutamate receptor antagonists. CIN-mediated glutamatergic responses exhibited a large contribution of NMDA-type glutamate receptors, distinguishing them from corticostriatal inputs. CIN-mediated glutamatergic responses were insensitive to antagonists of acetylcholine receptors and were not seen in mice lacking VGluT3. Our results indicate that CINs are capable of mediating fast glutamatergic transmission, suggesting a new role for these cells in regulating striatal activity.