Abstract
The concept of the excitatory action of GABA during early development is based on data obtained mainly in brain slice recordings. However, in vivo measurements as well as observations made in intact hippocampal preparations indicate that GABA is in fact inhibitory in rodents at early neonatal stages. The apparent excitatory action of GABA seems to stem from cellular injury due to the slicing procedure, which leads to accumulation of intracellular Cl− in injured neurons. This procedural artifact was shown to be attenuated through various manipulations such as addition of energy substrates more relevant to the in vivo situation. These observations question the very concept of excitatory GABA in immature neuronal networks.
Highlights
Brain slices are widely used to investigate basic processes of brain function
GABA IS NOT EXCITATORY IN THE INTACT BRAIN First, the early study performed in vivo, using intracellular recordings of hippocampal neurons in young kittens, suggested that inhibition is a predominant form of synaptic activity at early postnatal ages (Purpura et al, 1968)
It is difficult to state that GABA exerts an excitatory action when GABAA receptors (GABAAR) blockade leads to an increased activity in vivo
Summary
Brain slices are widely used to investigate basic processes of brain function. being a reduced preparation (i.e., there is no blood flow, oxygen levels are non-physiological, most in vivo metabolites are not present in the artificial cerebrospinal fluid), brain slices provide easier access to cellular phenomena than in vivo models. The concept of the excitatory action of GABA at early postnatal stages of development provides a particular example of correct observations performed in vitro which may not apply to the in vivo situation.
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