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[P2.09]: Developmental changes in GABAergic inhibitory mechanisms in human primary visual cortex throughout the lifespan
Author(s) -
Pinto J.,
Hornby K.,
Jones D.,
Murphy K.
Publication year - 2008
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2008.09.134
Subject(s) - citation , library science , cognitive science , humanities , computer science , psychology , art
Inhibitory systems play key roles in cortical circuit function and synaptic plasticity during both early neural development and the changes that accompany aging. GABA is the most widespread and abundant inhibitory neurotransmitter in cortex. While previous studies have examined GABAergic mechanisms in animal models, few have looked in human cortex at how thesemechanisms change across the lifespan. We completed a comprehensive study of both presynaptic and postsynaptic GABAergic mechanisms in human primary visual cortex (n = 30, age range: 20 days to 80 years). Using Western blot analysis of human postmortem tissue, we looked at the developmental profiles of the GABA synthesizing enzymes (GAD65/67), the GABA vesicular transporter (VGAT), GABAA receptor subunits (GABAAa1, a2, a3), the inhibitory modulating cannabinoid receptor (CB1), and the inhibitory receptor anchoring protein (Gephyrin). On the pre-synaptic side, GAD67 was constant across the lifespan, and GAD65 showed a modest developmental increase peaking during the teenage years. In contrast, VGAT expression was high before 1 year of age and then constant across the lifespan. On the post-synaptic side, GABAAa1 expression increased until the teen to young adult years, GABAAa2 expression decreased across the lifespan, and GABAAa3 expression stayed constant throughout life. These receptor changes reflect the developmental shift in relative subunit composition from immature (GABAAa2/a3) to mature (GABAAa1). Gephyrin expression increased gradually into the teen and young adult years then decreased with aging, suggesting a slow development of total GABAAR expression and age-related loss of these receptors. The inhibitory modulator CB1 was high until 1 year of age, then decreased into the teenage years, then remained relatively constant. Together, these results show modest presynaptic changes in GABAergic mechanisms across the lifespan and large postsynaptic changes in subunit composition during early development and age-related losses in total GABA receptor expression.