Original ArticleAbnormal Striatal GABA Transmission in the Mouse Model for the Fragile X Syndrome
Section snippets
Methods and Materials
Mice lacking fmr1 (fmr1-KO) (34), BC1 RNA (BC1-KO) (35), and both fmr1 and BC1 (fmr1-BC1-KO) were employed, along with respective age-matched wildtype (WT) counterparts (2–3 months old) for all the experiments. Animals were maintained in light:dark cycles of 12:12 hours and weaned after 21 days. The WT and KO mice used in these experiments were of different background strains: C57BL/6 for fmr1-KO mice, 129Sv/C57BL/6 for BC1-KO and fmr1-BC1-KO. Appropriate matching strains were used as controls.
Membrane Properties of Striatal Neurons
Whole-cell patch clamp recordings were obtained from striatal spiny neurons identified by morphologic and electrophysiologic criteria. Striatal spiny neurons had significantly smaller somata than interneurons (15–25 μm vs. 30–40 μm) and displayed high resting membrane potential (–81 ± 4 mV), action potential discharge with little adaptation during depolarizing current pulses, and, in voltage-clamp mode, a typical current-voltage relationship. These electrophysiologic properties were similar in
Discussion
Reduced expression of FMRP in FXS patients causes a wide range of neuropsychiatric manifestations, which include mental retardation, hyperactivity, and autism (27, 50, 51, 52). Abnormal activity of striatal neurons and frontostriatal projections seem to play critical roles in FXS, as suggested by structural and functional neuroimaging studies. Accordingly, larger than normal caudate nucleus volumes have been found in human FXS brains, and a clear association between reduced FMRP expression,
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This work is an equal contribution between the labs of Drs. Bagni and Centonze.