Voltage-gated sodium channels (NaCh) are colocalized with isoforms of the membrane-skeletal protein ankyrinG at axon initial segments, nodes of Ranvier, and postsynaptic folds of the mammalian neuromuscular junction. The role of ankyrinG in directing NaCh localization to axon initial segments was evaluated by region-specific knockout of ankyrinG in the mouse cerebellum. Mutant mice exhibited a progressive ataxia beginning around postnatal day P16 and subsequent loss of Purkinje neurons. In mutant mouse cerebella, NaCh were absent from axon initial segments of granule cell neurons, and Purkinje cells showed deficiencies in their ability to initiate action potentials and support rapid, repetitive firing. Neurofascin, a member of the L1CAM family of ankyrin-binding cell adhesion molecules, also exhibited impaired localization to initial segments of Purkinje cell neurons. These results demonstrate that ankyrinG is essential for clustering NaCh and neurofascin at axon initial segments and is required for physiological levels of sodium channel activity.

Reports that nitric oxide synthase (NOS) inhibition prevents the induction of long-term potentiation (LTP) have been controversial. Recent evidence suggests that NO may help to regulate the threshold for LTP induction. We have tested this hypothesis by examining the effects of stimulus frequency and train duration on synaptic plasticity in the presence of either NO donors or NOS inhibitors. Two different NO donors facilitated LTP induction by stimuli that normally produced only short-term potentiation, whereas NOS inhibitors blocked LTP to stimuli that normally produce small LTP. NO donors facilitated LTP induction even when NMDA receptors were blocked, indicating that NO need not act via NMDA receptors. NO donors and NOS inhibitors were without effect on long-term depression (LTD), suggesting that they act on a distinct potentiating mechanism. Thus, NO could contribute to the establishment of plasticity under physiologically relevant conditions by selectively increasing the probability of LTP induction.

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To examine the role of the medial zona incerta (m/I) in female sexual behavior, ovariectomized estrogen-and progesterone-treated female rats were tested for sexual receptivity after bilateral injections of the selective neurotoxin ibotenic acid (3 jig/0.3 id) directly into the mZI. These injections produced a significant attenuation of lordosis behavior in highly receptive females when compared with saline-injected controls. This decrease in sexual receptivity was also reflected in a significant increase of rejections of male mount attempts. However, these lesions did not abolish the display of lordosis behavior. In addition, the frequency of hopping and darting was decreased in ibotenic acid-injected females when compared with controls. Consistent with previous studies, these lesions also produced a transient impairment of drinking behavior (hypodipsia) typical of rats with large electrolytic lesions of the mZI. This study demonstrates that mZI neurons play a role in mediating sexual receptivity in the female rat. Collectively, these results suggest that in addition to the projection from the ventromedial nucleus of the hypothalamus to the midbrain central gray, the functional integrity of the mZI is of crucial importance for the expression of sexual receptivity in the female rat.