This document summarizes research investigating cortico-striatal projections in mice using the Allen Mouse Brain Connectivity Atlas. The researchers plan to compare projections from different cortical layers and regions to better understand basal ganglia circuitry. ImageJ software will be used to quantify projections from cerebral cortex to striatum and between cortical regions. Specifically, the strongest projections will be examined from divergent cortical maps to the striatum in a point-for-point manner. Multiple experiments will be compared to investigate projection patterns within the striatum.

1. Comparative Analysis Of The
Cortico-Striatal Relationship
Brian Smith, Christina Warner, Ronald Paletzki, Charles Gerfen
Laboratory 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: brian.smith4@nih.gov
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.
SSp
MO I
C and D
E and F
G and H

5. SSp
MOs
MOp