Deletion of Dlx1 results in reduced glutamatergic input to hippocampal interneurons

作者：Jones Daniel L; Howard MacKenzie A; Stanco Amelia; Rubenstein John L R; Baraban Scott C^*

来源：Journal of Neurophysiology, 2011, 105(5): 1984-1991.

DOI：10.1152/jn.00056.2011

• excitatory postsynaptic currents
• CA1
• CA3
• gamma-aminobutyric acid

Jones DL, Howard MA, Stanco A, Rubenstein JL, Baraban SC. Deletion of Dlx1 results in reduced glutamatergic input to hippocampal interneurons. J Neurophysiol 105: 1984-1991, 2011. First published February 16, 2011; doi:10.1152/jn.00056.2011.-Dlx transcription factors are important in the differentiation of GABAergic interneurons. In mice lacking Dlx1, early steps in interneuron development appear normal. Beginning at similar to 1 mo of age, primarily dendrite-innervating interneuron subtypes begin to undergo apoptosis in Dlx1(-/-) mice; this is accompanied by a reduction in GABAergic transmission and late-onset epilepsy. The reported reduction of synaptic inhibition is greater than might be expected given that interneuron loss is relatively modest in Dlx1(-/-) mice. Here we report that voltage-clamp recordings of CA1 interneurons in hippocampal slices prepared from Dlx1(-/-) animals older than postnatal day 30 (>P30) revealed a significant reduction in excitatory postsynaptic current (EPSC) amplitude. No changes in EPSCs onto interneurons were observed in cells recorded from younger animals (P9-12). Current-clamp recordings from interneurons at these early postnatal ages showed that interneurons in Dlx1(-/-) mutants were immature and more excitable, although membrane properties normalized by P30. Terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling, caspase-3, and NeuN staining did not reveal frank cell damage or loss in area CA3 of hippocampal sections from adult Dlx1(-/-) mice. Delayed interneuron maturation may lead to interneuron hyperexcitability, followed by a compensatory reduction in the strength of excitatory transmission onto interneurons. This reduced excitation onto surviving interneurons, coupled with the loss of a significant fraction of GABAergic inputs to excitatory neurons starting at P30, may underlie cortical dysrhythmia and seizures previously observed in adult Dlx1(-/-) mice.

• 出版日期2011-5