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Comparative Analysis Of The Cortico-Striatal Relationship
Brian Smith, Christina Warner, Ronald Paletzki, Charles GerfenLaboratory of Systems Neuroscience, NIMH
Future Directions• We are currently focusing on the C56BL/6J
mouse line, but plan on including specific Cre lines in our subsequent comparisons (Cux2-IRES-Cre, Rbp4-Cre_KL100). These Cre lines enrich projection within cortical layers 2/3 and 5, respectively.
• The projection data that we are using only shows single neuron paths, not trans-synaptic connectivity. Future research will try to integrate data showing this trans-synaptic connectivity, which in turn will give us a better understanding of basal ganglia circuitry and corresponding motor and behavioral actions.
Methods (cont.)• These projection data can be analyzed using
the computer software ImageJ. • The desired analysis includes:
I. quantification of projections originating in the cerebral cortex mapping into the striatum;
II. quantification of projections originating in the cortex mapping into other cortical regions;
III. comparison of experiments with projections originating in the same cortical area to study fine cortico-striatal topography;
IV. comparison of experiments with projections originating in separate cortical areas to study general cortico-striatal topography as well as cortico-cortical connectivity.
• Several ImageJ macros have been developed to analyze the nature of projection overlap within the striatum, as well as cortico-cortical connectivity.
Goals/Objectives• Investigate projection overlap within the
striatum and connectivity between cortical regions
• Utilize biological imaging software to provide a way to visualize cortico-striatal and cortico-cortical connectivity
Introduction• The basal ganglia forebrain system is involved
in voluntary motor actions, and is affected in several disorders including Parkinson’s and Huntington’s Disease.
• A major input to the basal ganglia are excitatory inputs from the cerebral cortex to the striatum.
• Projections originating in cortical areas generally map topographically to the striatum in a divergent manner, leading to overlap of the projections.
References• Website: ©2012 Allen Institute for Brain Science. Allen Mouse
Brain Connectivity Atlas [Internet]. Available from: http://connectivity.brain-map.org/
• Gerfen, C., Surmeier, DJ. Moduclation of striatal projection systems by dopamine. Annu Rev Neurosci. 2011; 34: 441-466.
• Schindelin, S., et al. Fiji: an open-source platform for biological-image analysis. Nature Methods. 2012; 9(7): 676-682.
Email: [email protected]
Specific Mapping (Point-for-Point)
Divergent Mapping
(Fig.1) Cortical neurons project divergently into the striatum in a topographic manner. A single neuron can have upwards of 10,000 connections within the striatum. In order to paint a clearer picture of how the cortex relates to the striatum, we will examine cortico-striatal projections in a Point-for-Point fashion, looking specifically at the strongest projections from the divergent map.
(Fig.2) These images show an example projection density map from the Allen Mouse Connectivity Database. The three-dimensional, user-controlled display can be accessed on the Allen Brain Institute’s website. The green dot indicates the injection site of the axonal tracer (in this case, the primary motor area), and the red crosshair indicates the target structure (the striatum).
Methods• The Allen Brain Institute Mouse Connectivity
Atlas contains projection data for over 180 C56BL/6J (wild-type) cortical axonal tracer experiments that can be downloaded from their website. This atlas is able to quantify projection overlap because all the data is normalized to a single brain space.
(Fig.3) Multiple experiments with projections originating from the cortex can be compared against each other. We first compared experiments with injection sites in the primary motor cortex (MOp) against each other (A), and then repeated this process for experiments with injection sites within the primary somatosensory cortex (SSp) (B). From these files we determined which experiments from MOp and SSp mapped into particular parts of the striatum. We then made cases comparing individual MOp and SSp experiments against each other to investigate the projection patterns within the striatum (C-H). A reference map of the injection sites for the experiments we investigated is provided (I). The colors of the icons indicate the colors assigned to the experiments compared in A-B, with our specific experiment comparisons (C-H) outlined.
SSpMO I
C and DE and FG and H
SSpMOsMOp
