Download presentation
Presentation is loading. Please wait.
1
The 2017 Dodge Young Investigator Award Lecture: Toward Novel Circuit Therapies for Autism
Audrey C. Brumback, MD, PhD Pediatric Neurology Volume 87, Pages (October 2018) DOI: /j.pediatrneurol Copyright © 2018 The Authors Terms and Conditions
2
FIGURE 1 Diverse etiologies of autism may converge on a common behavioral phenotype via shared changes in brain circuitry. Pediatric Neurology , 11-19DOI: ( /j.pediatrneurol ) Copyright © 2018 The Authors Terms and Conditions
3
FIGURE 2 Autism models exhibit deficits in the excitability of medial prefrontal cortex (mPFC) Layer 5 corticothalamic pyramidal neurons. (A) Mouse coronal brain slices demonstrating retrograde labeling of mPFC Layer 5 corticothalamic cells by injection of a fluorescently labeled retrogradely transported substance in mediodorsal (MD) thalamus (blue), and labeling of mPFC L5 intratelencephalic projection neurons by injection into the contralateral mPFC (red). (B) Examples of whole cell current clamp recordings from acute brain slices from autism models and control mice; responses are to −50 and +200 pA current steps. In mPFC L5 corticothalamic neurons, action potential (AP) frequency in response to current injection in autism models (light blue) compared with control subjects (dark blue). Scale bars = 200 ms. 20 mV. VPA = valproic acid; SAL = saline control; PL = prelimbic cortex. IL = infralimbic cortex. Pediatric Neurology , 11-19DOI: ( /j.pediatrneurol ) Copyright © 2018 The Authors Terms and Conditions
4
FIGURE 3 In autism model mice, mPFC DRD2-expressing cells activate abnormally during social encounters. Calcium imaging during social exploration in valproic acid mice (dark blue) or saline control subjects (light blue). Pediatric Neurology , 11-19DOI: ( /j.pediatrneurol ) Copyright © 2018 The Authors Terms and Conditions
5
FIGURE 4 Acute optogenetic manipulation of DRD2-expressing neuronal activity in mPFC modifies social exploration in autism model mice. Novel social exploration assay coupled with acute optogenetic activation or inactivation of medial prefrontal cortex (mPFC) neurons that express the dopamine type 2 receptor Drd2. Inhibition of mPFC DRD2+ neurons increased social exploration time. Activation of mPFC DRD2+ neurons decreased social exploration time. PL = prelimbic cortex; IL = infralimbic cortex. Pediatric Neurology , 11-19DOI: ( /j.pediatrneurol ) Copyright © 2018 The Authors Terms and Conditions
Similar presentations
© 2025 SlidePlayer.com. Inc.
All rights reserved.