Lecture 34 — Translational Autism NEU335.pdf

E empty m mouse c center control three chamber task e

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E = Empty M = Mouse C = Center Control
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Three chamber task E = Empty M = Mouse C = Center Most mice show a preference for the chamber containing a mouse. Not showing that “social preference” is considered an autism-like behavior. Control “Autistic”
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Autism models Inhibitory interneuron dysfunction in autism Altered Excitation-Inhibition (E-I) balance Intense world theory of autism Medial prefrontal cortex in social communication & “theory of mind” Autism as a “developmental disconnection syndrome”
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Interneuron dysfunction in autism Decreased interneuron #’s in human brain autopsies & autism model mice Interneuron dysfunction autistic features in mice # Interneurons Abnormal interneurons
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E I proposed by Merzenich & Rubenstein 2003 Excitatory / Inhibitory imbalance in autism epilepsy epileptiform discharges reviewed by Spence & Schneider 2009; Trauner 2015 + - + - Han et al, 2012 Yizhar & Fenno et al 2011 ion channel mutations reviewed by Blatt 2011, Rojas 2014 oscillations (interneurons) E I
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Autism models Inhibitory interneuron dysfunction in autism Altered Excitation-Inhibition (E-I) balance Intense world theory of autism Medial prefrontal cortex in social communication & “theory of mind” Autism as a “developmental disconnection syndrome”
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Intense world theory of autism “…a unifying hypothesis where the core pathology of the autistic brain is hyper- reactivity and hyper-plasticity of local neuronal circuits. Such excessive neuronal processing in circumscribed circuits is suggested to lead to hyper-perception, hyper-attention, and hyper-memory, which may lie at the heart of most autistic symptoms.” Rinaldi et al , 2008 Markram et al , Frontiers Neurosci, 2007 Enhanced LTP Experimental autism model: Increased # synaptic connections Weaker at baseline, but Stronger Long Term Potentiation Prefrontal cortex
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Autism Cells Circuits Behavior Genes
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Autism models Altered Excitation-Inhibition (E-I) balance Inhibitory interneuron dysfunction in autism Intense world theory of autism Medial prefrontal cortex in social communication & “theory of mind” Autism as a “developmental disconnection syndrome”
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Frith, 2001 Medial prefrontal cortex in social commun Medial prefrontal cortex in social communication & “theory of mind”
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  • Spring '16
  • Colgin
  • Asperger syndrome, Han

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