Journal
BRAIN STRUCTURE & FUNCTION
Volume 224, Issue 1, Pages 73-97Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00429-018-1762-6
Keywords
Anterograde; Fos-related antigen; Rat; Synaptophysin
Categories
Funding
- NIH [K99/R00 HL122454, R01 MH049698, R01 MH101729]
- American Heart Association Fellowship
- Colorado State University Molecular, Cellular and Integrative Neuroscience program
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [K99HL122454, R00HL122454] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH101729, R01MH049698] Funding Source: NIH RePORTER
Ask authors/readers for more resources
The medial prefrontal cortex is critical for contextual appraisal, executive function, and goal-directed behavior. Additionally, the infralimbic (IL) subregion of the prefrontal cortex has been implicated in stress responding, mood, and fear memory. However, the specific circuit mechanisms that mediate these effects are largely unknown. To date, IL output to the limbic forebrain has been examined largely qualitatively or within a restricted number of sites. To quantify IL presynaptic input to structures throughout the forebrain, we utilized a lentiviral construct expressing synaptophysin-mCherry. Thus, allowing quantification of IL efferents that are specifically synaptic, as opposed to fibers of passage. Additionally, this approach permitted the determination of IL innervation on a sub-structural level within the multiple heterogeneous limbic nuclei. To examine the functional output of the IL, optogenetic activation of IL projections was followed by quantification of neuronal activation throughout the limbic forebrain via fos-related antigen (Fra). Quantification of synaptophysin-mCherry indicated that the IL provides robust synaptic input to a number of regions within the thalamus, hypothalamus, amygdala, and bed nucleus of the stria terminalis, with limited input to the hippocampus and nucleus accumbens. Furthermore, there was high concordance between structural connectivity and functional activation. Interestingly, some regions receiving substantial synaptic input did not exhibit significant increases in Fra-immunoreactivity. Collectively, these studies represent a step toward a comprehensive and quantitative analysis of output circuits. This large-scale efferent quantification or projectome' also opens the door for data-driven analyses of the downstream synaptic mechanisms that mediate the integrative aspects of cortico-limbic interactions.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available