Lee-Ming Kow

Ascending tracts of the lateral columns of the rat spinal cord: A study using the silver impregnation and horseradish peroxidase techniques

Abstract The location of projection areas and cells of origin of the ascending fiber tracts of the spinal cord lateral columns were examined in the rat. Projection areas were localized after unilateral microtransection of lateral column fibers at C2 or T10, using silver impregnation of preterminal and fiber degeneration. Cells of origin were localized by unilateral microtransection and subsequent application of horseradish peroxidase (HRP). Two groups of fibers projected to the dorsal medulla. One group projected to nucleus intercalatus, commissuralis, and the dorsal column nuclei. The second group projected via the inferior cerebellar peduncle to the vestibular complex, with additional fibers continuing dorsally to the cerebellum. The most extensive system of ascending fibers projected to the reticular formation. Most spinoreticular fibers coursed through the ventral hindbrain and projected to the lateral reticular nucleus, ventral reticular nucleus, nucleus gigantocellularis, and nucleus subceruleus. Spinotectal and spinocentral gray fibers coursed through the ventral portion of the medulla and then dorsally through the pons. Spinocentral gray fibers projected to the caudal portion of the central gray matter, ipsilaterally. Spinotectal fibers projected to the intercollicular nucleus and adjacent portions of the superior colliculus, bilaterally. Two projections to the thalamus were observed after anterolateral column transection. Preterminal degeneration was observed in the ventrobasal complex ipsilaterally, and bilaterally in the intralaminar nuclei. In conjunction with previous results the present HRP data suggest that the cells of origin of spinothalamic tract fibers were situated in laminae IV, V, and VI. The location of spinal cord cells of origin of additional ascending tracts is discussed.

Effects of Estrogen Treatment on the Size of Receptive Field and Response Threshold of Pudendal Nerve in the Female Rat

Receptive fields and response thresholds were determined by stimulation with a camel hair brush and von Frey hairs during recording from a specific branch of the pudendal nerve, in untreated and estro

Early membrane estrogenic effects required for full expression of slower genomic actions in a nerve cell line

Interpretations of steroid hormone actions as slow, nuclear, transcriptional events have frequently been seen as competing against inferences of rapid membrane actions. We have discovered conditions where membrane-limited effects potentiate later transcriptional actions in a nerve cell line. Making use of a two-pulse hormonal schedule in a transfection system, early and brief administration of conjugated, membrane-limited estradiol was necessary but not sufficient for full transcriptional potency of the second estrogen pulse. Efficacy of the first pulse depended on intact signal transduction pathways. Surprisingly, the actions of both pulses were blocked by a classical estrogen receptor (ER) antagonist. Thus, two different modes of steroid hormone action can synergize.

Effects of medial hypothalamic lesions on the lordosis response and other behaviors in female golden hamsters

Abstract The lordosis response in ovariectomized, hormone-primed females was measured in repeated weekly tests before and after bilateral lesions of various medial hypothalamic regions. Changes in body weight, frequency of vaginal marking, and agonistic behavior were also recorded. Forty-two females were divided into five groups based on lesion location: (1) medial preoptic (MPO), (2) medial anterior hypothalamus (MAH), (3) dorsomedial nucleus-dorsal premammillary nucleus (DM-DPM), (4) dorsal ventromedial nucleus (Dorsal VMN), (5) medial basal hypothalamus (MBH). Unoperated control females were tested in an identical manner. Only lesions in the region of the ventromedial nucleus eliminated lordosis. Lesions which disrupted lordosis also increased agonistic behavior in male-female pairs. The frequency of vaginal marking was reduced by lesions in the MPO, MAH, and Dorsal VMN groups. Rapid weight increases and obesity were also seen following certain medial hypothalamic lesions, however no significant correlations were found between degree of weight change and degree of lordosis deficit. A quantitative analysis of VMN damage revealed a relatively low, but statistically significant positive correlation between degree of VMN damage and lordosis deficits. There were no significant correlations between degree of VMN damage and weight change.

Estradiol Regulation of Nitric Oxide Synthase mRNAs in Rat Hypothalamus

Expression and estrogen regulation of the genes for nitric-oxide (NO)-synthesizing enzymes (NO synthase, NOS) were investigated by in situ hybridization. This study focused on regions of the hypothalamus that contain estrogen receptors and regulate specific neuroendocrine functions related to female sexual behavior and food intake, among others. Ovariectomized (OVX) rats were treated with vehicle or 3 micrograms/100 g estradiol benzoate (EB) for 7 days. Brains were sectioned and hybridized with antisense riboprobes for neuronal NOS, macrophage NOS and endothelial NOS. In the hypothalamus, mRNA was clearly detectable only for the neuronal NOS with the probes used. A strong hybridization signal was observed in the supraoptic paraventricular and ventromedial nuclei (SON, PVN and VMN, respectively). Quantitative analysis showed an increase in neuronal NOS mRNA in the VMN of the OVX rats treated with EB. The increase was mainly in the ventrolateral aspect of the VMN. No significant changes were observed in the hypothalamic SON and PVN. The data suggest that the expression of neuronal NOS mRNA in VMN can be regulated by estrogen.

Roles of second-messenger systems and neuronal activity in the regulation of lordosis by neurotransmitters, neuropeptides, and estrogen: A review

Many neurotransmitters and neuropeptides can affect the rodent feminine sexual behavior, lordosis, when administered in the ventromedial hypothalamus (VMH), midbrain central gray (MCG), or other brain regions. A survey of the electrophysiological and biochemical actions of these neural agents revealed that there is a very consistent association between lordosis facilitation with both the activation of the phosphoinositide (PI) pathway and the excitation of VMH and MCG neurons. In contrast, lordosis inhibition is associated, less consistently, with alterations of the adenylate cyclase (AC) system and the inhibition of neuronal activity. The findings that lordosis could be facilitated by going beyond membrane receptors and directly activating the PI pathway, suggest that this second-messenger pathway is a common mediator for the lordosis-facilitating agents. Furthermore, as in the case of stimulating membrane receptors, direct activation of this common mediator also requires estrogen priming for lordosis facilitation. Therefore, it is likely that the PI pathway is modulated by estrogen in the permissive action of estrogen priming. Indeed, a literature review shows that estrogen can affect selective isozymes of key enzyme families of the PI pathway at various levels. Such selective modulations, at several levels, could easily alter the course of a PI cascade; thence, the eventual functional outcome. These findings prompt us to propose that estrogen enables lordosis to be facilitated by a selective modulation of the PI pathway.

Estrogen effects on neuronal responsiveness to electrical and neurotransmitter stimulation: an in vitro study on the ventromedial nucleus of the hypothalamus

To investigate the effects of estrogen on the activity of the neurons in the hypothalamic ventromedial nucleus (VMN), the single-unit activity was recorded from in vitro brain tissue slices prepared from ovariectomized rats that were either treated or untreated with estrogen. In tissue slices continuously perifused with estrogen-free solution, half of the 348 VMN neurons studied were silent or nearly silent, and the rest fired spontaneously at low rates. Electrical stimulation of the periventricular region medial to the VMN evoked not only 3 types of orthodromic responses, but also antidromic responses from many VMN neurons, indicating that the VMN and the periventricular region are intimately and reciprocally connected. Neuronal responses to a battery of 6 neurotransmitters were studied by microinjecting 50 microliters of a transmitter solution directly into the chamber where the tissue slice was being continuously perifused. When effective, glutamate (Glut) was almost exclusively excitatory; acetylcholine (ACh) and norepinephrine (NE) could be excitatory and/or inhibitory; 5-hydroxytryptamine (5-HT) and dopamine (DA) were predominantly inhibitory; and gamma-amino-butyric acid (GABA) was exclusively inhibitory on neuronal activity. The overall resting neuronal activity and responses to the transmitter were very similar to those observed in in vivo studies, indicating that, for VMN at least, in vitro tissue slices can serve as a simplified model for studying neuronal activity and responses. Comparisons of results between estrogen-treated and untreated preparations showed that chronic, in vivo estrogen treatments, while having no effect on resting firing rate, selectively facilitated the responsiveness of silent (but not spontaneously active) neurons to excitatory orthodromic inputs, and the responsiveness to the excitatory action of ACh, the overall action of NE and the inhibitory action of 5-HT. These selective estrogen effects would no doubt alter the input-output relationships of VMN neurons evoked by the orthodromic inputs and ACh, NE and 5-HT. Since the VMN is crucial to many biological functions, and the cholinergic, adrenergic and serotonergic inputs to the ventromedial hypothalamus are involved in the estrogenic regulation of sexual behavior, reproductive neuroendocrine, and other biological functions, the alteration of the input-output relationships evoked by the orthodromic and transmitter inputs would affect the regulation of many functions.

Female oxytocin gene-knockout mice, in a semi- natural environment, display exaggerated aggressive behavior

Compared to results from a generation of neuropharmacological work, the phenotype of mice lacking the oxytocin (OT) peptide gene was remarkably normal. An important component of the current experiments was to assay OT‐knockout (OTKO) and wild‐type (WT) littermate control mice living under controlled stressful conditions designed to mimic more closely the environment for which the mouse genome evolved. Furthermore, our experimental group was comprised of an all‐female population, in contrast to previous studies which have focused on all‐male populations. Our data indicated that aggressive behaviors initiated by OTKO during a food deprivation feeding challenge were considerably more intense and diverse than aggressive behaviors initiated by WT. From the measures of continuous social interaction in the intruder paradigm, it emerged that OTKO mice were more offensively aggressive (attacking rumps and tails) than WT. In a test of parental behaviors, OTKO mice were 100% infanticidal while WT were 16% infanticidal and 50% maternal. Finally, ‘alpha females’ (always OTKO) were identified in each experiment. They were the most aggressive, the first to feed and the most dominant at nesting behaviors. Semi‐natural environments are excellent testing environments for elucidating behavioral differences between transgenic mice and their WT littermates which may not be ordinarily discernible. Future studies of mouse group behavior should include examining female groupings in addition to the more usual all‐male groups.

Concepts and mechanisms of generalized central nervous system arousal.

A concept of generalized arousal of the CNS is presented and given an operational definition that leads to quantitative physical measures. Because this primitive arousal function underlies all motivated behavioral responses, cognitive functions, and emotional expression, disorders of generalized arousal can be associated with a large number of problems in medicine and public health, including vegetative states, attentional disorders, depression, occupational hazards, and problems with sleep and anesthesia. Some of its known mechanisms are briefly reviewed, at the levels of neuroanatomy, neurophysiology, and functional genomics. Generalized arousal contributes to the excitement and the activation of behaviors during specific arousal states. Data are summarized for four genomic/neurochemical systems through which changes in generalized arousal could affect sexual arousal, two of which heighten, and the other two of which reduce arousal.

Sensory requirement for the lordosis reflex in female rats

(1) Visual, auditory and olfactory input were not necessary for the performance of the lordosis reflex by female rats. Since taste is not involved in this behavior, somatosensory input must be sufficient for triggering the lordosis reflex. (2) Surgical cutaneous denervation markedly reduced the frequency and strength of lordosis. The most effective operation denervated the perineum, tailbase, posterior rump and ventral flanks. This pattern of results agrees with film observations and manual stimulation of lordosis. (3) Effects of surgical cutaneous denervation were confirmed in experiments with local anesthesia produced by subcutaneous procaine injections. (4) It is deduced that cutaneous mechanoreceptors in specific regions of hairy skin of the female rat play a crucial role in triggering the lordosis reflex.