Selective postnatal excitation of neocortical pyramidal neurons results in distinctive behavioral and circuit deficits in adulthood
Autor: | Madison L. Waddell, Christopher I. Moore, Akash Pal, William E. Medendorp, Ute Hochgeschwender, Mansi Prakash, Emmanuel L. Crespo, Andreas Bjorefeldt |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
EMX1 02 engineering and technology Optogenetics Inhibitory postsynaptic potential Article Behavioral Neuroscience 03 medical and health sciences Developmental Neuroscience Cellular neuroscience Cortex (anatomy) medicine lcsh:Science Prefrontal cortex Dopamine transporter Multidisciplinary biology food and beverages 021001 nanoscience & nanotechnology 030104 developmental biology medicine.anatomical_structure nervous system Cellular Neuroscience biology.protein lcsh:Q 0210 nano-technology Neuroscience Parvalbumin |
Zdroj: | iScience, Vol 24, Iss 3, Pp 102157-(2021) iScience |
ISSN: | 2589-0042 |
Popis: | Summary In genetic and pharmacological models of neurodevelopmental disorders, and human data, neural activity is altered within the developing neocortical network. This commonality begs the question of whether early enhancement in excitation might be a common driver, across etiologies, of characteristic behaviors. We tested this concept by chemogenetically driving cortical pyramidal neurons during postnatal days 4–14. Hyperexcitation of Emx1-, but not dopamine transporter-, parvalbumin-, or Dlx5/6-expressing neurons, led to decreased social interaction and increased grooming activity in adult animals. In vivo optogenetic interrogation in adults revealed decreased baseline but increased stimulus-evoked firing rates of pyramidal neurons and impaired recruitment of inhibitory neurons. Slice recordings in adults from prefrontal cortex layer 5 pyramidal neurons revealed decreased intrinsic excitability and increased synaptic E/I ratio. Together these results support the prediction that enhanced pyramidal firing during development, in otherwise normal cortex, can selectively drive altered adult circuit function and maladaptive changes in behavior. Graphical abstract Highlights • BL-OG allows chemogenetic activation and optogenetic interrogation in the same animal • Developmental hyperexcitation in normal mice leads to neurodevelopmental disorders • In these mice adult neurons show reduced baseline activity and increased excitability • Reduced activity-triggered coherence and altered oscillations in cortex and striatum Behavioral Neuroscience; Developmental Neuroscience; Cellular Neuroscience |
Databáze: | OpenAIRE |
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