NMDA receptor antagonists extend the sensitive period for imprinting

Efforts to determine and understand the causes of autism are currently hampered by a large disconnect between recent molecular genetics findings that are associated with the condition and the core behavioral symptoms that define the condition. In this perspective piece, we propose a systems biology framework to bridge that gap between genes and symptoms. The framework focuses on basic mechanisms of socialization that are highly-conserved in evolution and are early-emerging in development. By conceiving of these basic mechanisms of socialization as quantitative endophenotypes, we hope to connect genes and behavior in autism through integrative studies of neurodevelopmental, behavioral, and epigenetic changes. These changes both lead to and are led by the accomplishment of specific social adaptive tasks in a typical infant's life. However, based on recent research that indicates that infants later diagnosed with autism fail to accomplish at least some of these tasks, we suggest that a narrow developmental period, spanning critical transitions from reflexive, subcortically-controlled visual behavior to interactional, cortically-controlled and social visual behavior be prioritized for future study. Mapping epigenetic, neural, and behavioral changes that both drive and are driven by these early transitions may shed a bright light on the pathogenesis of autism.

show abstract

“…Strikingly, NMDA receptor antagonists substantially extend the sensitive period for imprinting (Parsons and Rogers, 2000). …”

Section: Endophenotypes and Model Systemsmentioning

confidence: 99%

Social visual engagement in infants and toddlers with autism: Early developmental transitions and a model of pathogenesis

Klin

Shultz

Jones

2015

Neuroscience & Biobehavioral Reviews

153

132

View full text Add to dashboard Cite

show abstract

“…Increases in CA 2þ -dependent glutamate release are found after a one-trial passive avoidance task or imprinting training (Tsukada et al, 1999;Daisley and Rose, 2002;Meredith et al, 2004). Chicks receiving MK-801 prolong the sensitive critical period for imprinting (Parsons and Rogers, 2000).…”

Section: Distribution Of Vglut2mentioning

confidence: 99%

Immunohistochemical localization of vesicular glutamate transporter 2 (vGluT2) in the central nervous system of the pigeon (Columba livia)

Atoji

2011

J of Comparative Neurology

View full text Add to dashboard Cite

Glutamatergic neurons are distributed widely in the telencephalic pallium of birds, but their targets are unknown. In the present study, a polyclonal antibody was produced against pigeon vesicular glutamate transporter 2 (vGluT2) and was used for Western blot and immunohistochemistry to detect projection targets of glutamatergic neurons in the pigeon central nervous system. The molecular weight of vGluT2 was measured at 65 kDa. vGluT2 immunoreactivity was observed in neuropil, but not in neuronal cell bodies or glia. Immunoreactive neuropil generally appeared homogeneous, but fine granules or puncta were found in many areas or nuclei. The telencephalon showed strong immunoreactivity, except for the globus pallidus. In particular, the mesopallium and hippocampal formation revealed the most intense immunostaining. In the diencephalon, vGluT2 immunoreactivity was intense in the dorsal thalamus and hypothalamus. In the midbrain, strong immunostaining was seen in the periaqueductal gray, the dorsal part of the lateral mesencephalic nucleus, and the isthmo-optic nucleus. The optic tectum showed moderate immunoreactivity. In the cerebellar cortex, glomeruli in the granular layer were intensely immunoreactive, and the molecular layer showed intensely homogeneous immunostaining. In the caudal brainstem, the cochlear magnocellular and angular nuclei showed strongly immunoreactive puncta around neuronal cell bodies. In the spinal cord, the dorsal horn revealed moderate immunoreactivity and the marginal nucleus was strongly immunoreactive. Ultrastructural observations revealed that vGluT2 immunoreactivity is localized in asymmetric, presynaptic terminals. The present results indicate an extensive distribution of glutamatergic projections and circuits in the avian central nervous system.

show abstract

“…Such an extension of the imprinting period is limited, however, since chicks kept in the dark for the first days after hatching will imprint up to about day 4 or 5 of life provided that they are then taken into the light and exposed to an imprinting stimulus but they will not imprint if held in the dark for longer (Parsons, 1994), unless they are treated with pharmacological agents that modulate the number or sensitivity of glutamate receptors in the brain (McCabe, Davey, & Horn, 1992;Parsons & Rogers, 1997. For example, chicks that have been treated with ketamine or MK-801, both drugs which act on glutamate receptors, within about 10 hours after hatching will imprint on day 8, whereas controls show no ability to imprint at this age (Parsons & Rogers, 2000).…”

Section: Sensitive Period For Imprintingmentioning

confidence: 99%

“…The two sensitive periods are linked. In fact, light stimulation of the embryo changes the lateralized levels of glutamate receptor binding (Johnston, Bourne, Stewart, Rogers, & Rose, 1997) and the levels of these receptors in IMM are important for imprinting memory formation (Johnston, Rogers, & Dodd, 1995;Johnston, Rogers, & Johnston, 1993;Parsons & Rogers, 2000).…”

Section: Sensitive Period For Imprintingmentioning

confidence: 99%

Interactive Contributions of Genes and Early Experience to Behavioral Development

Rogers

2010

Handbook of Developmental Science, Behavior, and Genetics

View full text Add to dashboard Cite

NMDA receptor antagonists extend the sensitive period for imprinting

Cited by 9 publications

References 30 publications

Social visual engagement in infants and toddlers with autism: Early developmental transitions and a model of pathogenesis

Social visual engagement in infants and toddlers with autism: Early developmental transitions and a model of pathogenesis

Immunohistochemical localization of vesicular glutamate transporter 2 (vGluT2) in the central nervous system of the pigeon (Columba livia)

Interactive Contributions of Genes and Early Experience to Behavioral Development

Contact Info

Product

Resources

About