Selective Postnatal Excitation of Neocortical Pyramidal Neurons Results in Distinctive Behavioral and Circuit Deficits in Adulthood. Medendorp, W. E.; Pal, A.; Waddell, M.; Björefeldt, A.; Moore, C. I.; and Hochgeschwender, U. January 2020.
Selective Postnatal Excitation of Neocortical Pyramidal Neurons Results in Distinctive Behavioral and Circuit Deficits in Adulthood [link]Paper  doi  abstract   bibtex   3 downloads  
Summary In leading models of Autism Spectrum Disorder, and in human data, the efficacy of outgoing cortical connectivity transitions from overly exuberant to languid from early development to adulthood. This transition begs the question of whether the early enhancement in excitation might be a common driver, across etiologies, of these symptoms. We directly tested this concept by chemogenetically driving neuronal activity in neocortical 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, impaired recruitment of inhibitory neurons and reduced cortico-striatal communication. These results directly support the prediction that changed firing in developing circuits irreversibly alters adult circuit function that leads to maladaptive changes in behaviors. This experimental approach offers a valuable platform to study the impact of disruption of developmental neural activity on the formation and function of adult neural circuits and behavior.
@unpublished{medendorp_selective_2020,
	type = {{bioRxiv}},
	title = {Selective {Postnatal} {Excitation} of {Neocortical} {Pyramidal} {Neurons} {Results} in {Distinctive} {Behavioral} and {Circuit} {Deficits} in {Adulthood}},
	url = {http://biorxiv.org/lookup/doi/10.1101/2020.01.18.911347},
	abstract = {Summary
          
            In leading models of Autism Spectrum Disorder, and in human data, the efficacy of outgoing cortical connectivity transitions from overly exuberant to languid from early development to adulthood. This transition begs the question of whether the early enhancement in excitation might be a common driver, across etiologies, of these symptoms. We directly tested this concept by chemogenetically driving neuronal activity in neocortical 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, impaired recruitment of inhibitory neurons and reduced cortico-striatal communication. These results directly support the prediction that changed firing in developing circuits irreversibly alters adult circuit function that leads to maladaptive changes in behaviors. This experimental approach offers a valuable platform to study the impact of disruption of developmental neural activity on the formation and function of adult neural circuits and behavior.},
	language = {en},
	urldate = {2020-05-29},
	author = {Medendorp, William E. and Pal, Akash and Waddell, Madison and Björefeldt, Andreas and Moore, Christopher I. and Hochgeschwender, Ute},
	month = jan,
	year = {2020},
	doi = {10.1101/2020.01.18.911347},
	keywords = {BiolumHub, LMO3},
}
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