Hypothalamic influences on the electrical activity of the olfactory pathway

By means of evoked potentials a direct efferent connection was found to run from the posterior hypothalamus and medial forebrain bundle to primary olfactory structures (olfactory bulb, olfactory tubercle and prepyriform cortex). The pathway from the hypothalamus to the olfactory bulb follows in the lateral olfactory tract at a conduction velocity 5–10 m/sec. The olfactory tubercle functions as a relay station for the efferent fibers from various sources, running to the olfactory bulb. In animals with electrodes chronically implanted in the olfactory structures, hypothalamic stimulation gives rise to a prolonged train of hypersynchronous bursts of activity (40–50 Hz), which resemble the arousal reaction. This response is modified by transecting the cervical sympathetic trunk. By pathways still to be defined, potentials are evoked in the olfactory bulb by stimulation of the cervical sympathetic trunk and the termination of these sympathetic fibers shows a common postsynaptic neuronal pool with axons of hypothalamic origin. Epinephrine topically applied to the olfactory mucosa induced hypersynchronous activity in olfactory structures, quite similar to that consequent to hypothalamic stimulation. These results suggest a multichanneled hypothalamic modulation of olfactory input.     

Vagus nerve stimulation modifies the electrical activity of the olfactory bulb

Evoked potential and unit activity recording techniques were used to study the effects of the vagus nerve stimulation on the olfactory bulb. A biphasic potential was evoked in the olfactory bulb by a single pulse delivered to the vagus nerve. Half of the neurons studied decreased discharge frequency after single pulse or train stimulation. The interval during which neurons ceased activity corresponded to the duration of the negative wave of the evoked potential. Responsive neurons were marked with horseradish peroxidase applied iontophoretically. Responsive neurons were located in the periglomerular layer of the olfactory bulb. These results suggest the existence of a vagus nerve-olfactory bulb pathway. The functional significance of this pathway is discussed.     

Olfactory pathway evoked potentials in response to hypothalamic stimulation

GUEVARA-AGUILAR, R. AND H. U. AGUILAR-BATURONI. Olfactory pathway evoked potentials in response tohypothalamic stimulation. BRAIN RES. BULL. 3(5) 467–474, 1978.—Ipsilateral and contralateral stimulation of lateral, ventromedial and posterior hypothalamic nuclei produced evoked responses in the olfactory bulb and in the prepyriform cortex. No differences in the latencies were found by stimulation of each nucleus in the homo and contralateral olfactory structures. The high amplitude of the fast component (N1) was obtained with stimuli applied to the ventral zones and the slow components (N2,N3) were obtained with more dorsal stimulation. An ipsilateral pathway is indicated at the supramammillary and posterior commissure level, since severing these structures abolishes the evoked responses. A bilateral projection is proposed for the olfactory bulb.     

Role of the paraventricular nucleus in the projection from the nucleus of the solitary tract to the olfactory bulb

Electrophysiological experiments were performed on anesthetized rats to determine the effects of lesions of the paraventricular nucleus on the amplitude of evoked potentials recorded in the periglomerular layer of the olfactory bulb after nucleus of the solitary tract electrical stimulation. Lesions of the paraventricular nucleus enhance the amplitude of both the positive and negative components of the evoked potential in the olfactory bulb. The pathway from the paraventricular nucleus to the olfactory bulb seems to exert a suppressive influence over the projection from the nucleus of the solitary tract to the olfactory bulb under these conditions.     

Sexual dimorphic stages affect both proliferation and serotonergic innervation in the adult rostral migratory stream

One of the sexual dimorphic differences in adult rodents is neural proliferation. Here we demonstrate that physiological hormone stages can modulate this proliferation in the adult forebrain. Female mice, both pregnant and synchronized in oestrus, exhibited higher proliferating cell percentages than males in both the rostral migratory stream (RMS) and the olfactory bulb (OB). Moreover, although the hormonal component also influenced the subventricular zone (SVZ), no differences in proliferation were observed in this region. In addition, both groups of females had higher numbers of serotonergic fibres in these regions. Serotonin may therefore be related to the mechanism of action by which hormones can affect cell proliferation of this brain region. We also evaluated cell death in the SVZ in males and females, finding that this was higher in the former. Taken together, our results support the idea that in female rodents more neuroblasts are able to reach the RMS and then proliferate, apoptosis being an additional mechanism affecting the low proliferation of cells in the RMS and OB in males. Thus, proliferation in the RMS is influenced by sexual dimorphism.     

Ontogeny of thymidine kinase and DNA in the hypothalamus and cerebral cortex of the rat: Effects of neonatal estrogen

Developmental patterns of activity for thymidine kinase and DNA content were determined for the hypothalamus and cerebral cortex of the female rat during the first 3 postnatal weeks. The DNA content and thymidine kinase activity for both brain structures were maximal at ages 1 and 3 days, respectively. Total DNA content for the hypothalamus significantly increased 21% between ages 1 and 21 days. Administration of 17β-estradiol benzoate (EB) during the sexually critical period of brain differentiation had no effect on thymidine kinase in either brain structure. However, a transient and highly significant decrease in DNA content occurred in the hypothalamus of the 2-day-old EB-treated rat. These data indicate that (a) DNA synthesis occurs in the postnatal hypothalamus, (b) DNA synthesis in the hypothalamus and cortex is not tightly coupled to the activity of thymidine kinase and, (c) the EB-induced decrease in hypothalamic DNA is not related to changes in thymidine kinase.     

Characterization and anatomical distribution of selective long-term potentiation in the olfactory forebrain

High-frequency stimulation of the granule cell layer of the olfactory bulb (OB) has previously been shown to result in a form of long-term potentiation in the piriform cortex (PC) that is selective to late components of the potential evoked in the PC58. This phenomenon was explored in male Long-Evans rats with chronically implanted electrodes by recording potentials evoked in the OB and in various sites in the ipsilateral and contralateral PC before and after repeated high-frequency stimulation of the OB. Recordings at all sites exhibited a gradually developing potentiation that was selective to late components of the evoked potential. In the OB and ipsilateral PC this potentiation had an overt long-term component that lasted for days, and all sites exhibited a latent potentiation that enabled the reestablishment of substantial levels of potentiation by mild patterns of stimulation that had no effect in control animals. No potentiation of the population EPSP representing input from the lateral olfactory tract to the PC was seen. Available evidence concerning the neuronal elements activated by the stimulation and the neuronal events likely to underlie the potentiated components of the evoked potentials suggests that this potentiation may represent an enhancement of inhibitory interactions within the PC and between the PC and OB.     

A role for the androgen receptor in the sexual differentiation of the olfactory system in mice

Olfactory signals play a central role in the identification of a mating partner in rodents, and the behavioral response to these cues varies markedly between the sexes. As several other sexually dimorphic traits, this response is thought to differentiate as a result of exposure of the developing individual to gonadal steroids, but both the identity of the specific steroid signal and the neural structures targeted for differentiation on this particular case are largely unknown. The present review summarizes results obtained in our lab using genetic males affected by the testicular feminization syndrome (Tfm) as experimental model, and that led to the identification of a role for non-aromatized gonadal steroids acting through the androgen receptor (AR) in the differentiation of olfactory cues processing in mice. The existing literature about AR-mediated sexual differentiation of the CNS in animal models is discussed, along with potential targets for the action of non-aromatized gonadal steroids in either one of the subsystems that detect and process olfactory information in rodents.     

Sex differences in the human olfactory system

The olfactory system (accessory) implicated in reproductive physiology and behavior in mammals is sexually dimorphic. These brain sex differences present two main characteristics: they are seen in neural circuits related to sexual behavior and sexual physiology and they take one of two opposite morphological patterns (male>female or female>male). The present work reports sex differences in the olfactory system in a large homogeneous sample of men (40) and women (51) using of voxel-based morphology. Gray matter concentration showed sexual dimorphism in several olfactory regions. Women have a higher concentration in the orbitofrontal cortex involving Brodmann's areas 10, 11 and 25 and temporomedial cortex (bilateral hippocampus and right amygdala), as well as their left basal insular cortex. In contrast, men show a higher gray matter concentration in the left entorhinal cortex (Brodmann's area 28), right ventral pallidum, dorsal left insular cortex and a region of the orbitofrontal cortex (Brodmann's area 25). This study supports the hypothesis that the mammalian olfactory system is a sexually dimorphic network and provides a theoretical framework for the morphofunctional approach to sex differences in the human brain.     

Transection of the rat olfactory nerve increases glial fibrillary acidic protein immunoreactivity from the olfactory bulb to the piriform cortex

Astrocytic glial fibrillary acidic protein (GFAP) immunoreactivity in response to retrograde changes of motoneurons after axotomy has been the subject of a number of reports. In contrast, this study examined the astrocytic GFAP immunoreactivity in response to axotomy in a sensory system, the adult rat olfactory system. The purpose of this study was to determine, by immunolabeling GFAP, the extent and transience of astrocytic reactivity in the olfactory system. Unilateral transection of the olfactory nerve fascicles was performed intracranially at the level of the cribriform plate. Rats were allowed to survive from 24 hours to 1 month after axotomy. GFAP immunolabeling was examined throughout the rat olfactory system using the peroxidase-anti-peroxidase method. After axotomy, a transient increase occurred in the astrocytic GFAP immunoreactivity in the ipsilateral olfactory system. The greatest enhancement of GFAP immunoreactivity in the olfactory system occurred at 48 hours post-axotomy. Increased GFAP immunoreactivity occurred not only along the axons and synaptic endings of the injured primary olfactory neurons, but also along the dendrites, cell bodies, axons, and synaptic endings of the secondary sensory neurons. The increased GFAP immunoreactivity was specifically associated with the anatomical distribution pathways of the primary and secondary olfactory neurons. Increased GFAP immunoreactivity was not altered until 14 days post-axotomy. At 1 month post-axotomy, GFAP immunoreactivity returned to control levels. The time course and transience of increased GFAP immunoreactivity closely correlates with the time course of rat primary olfactory neuronal degeneration and regeneration after axotomy.(ABSTRACT TRUNCATED AT 250 WORDS)     

部分神经肌肉阻滞及不同麻醉深度对经颅电刺激运动诱发电位的影响

目的 将肌松监测和脑电监测相结合,探索在部分神经肌肉阻滞及不同麻醉深度对经颅电刺激运动诱发电位(TceMEP)的影响.方法 12例行神经外科手术的患者术中行TceMEP监测,同时监测脑电图和5个成串刺激(TOF),计算爆发抑制比(BSR)和T4与T1比值,在BSR=0、肌松完全恢复后记录TceMEP基线;调节异丙酚和肌松药剂量,分别在肌松恢复、0.25＜BSR＜0.5和BSR＞0.75以及BSR=0、T4/T1为25%时记录TceMEP并评估刺激时患者出现体动的情况.结果 基线时患者出现体动率较高(9/10),在肌松恢复、0.25＜BSR＜0.5和BSR＞0.75两种情况下体动发生率降低(1/10和0/10),TceMEP波幅较基线时下降明显(P＜0.05和P＜0.01);部分肌松且BSR=0时TceMEP波幅较基线时相差不多(P＞0.05),10例中仅1例出现体动;各种情况下的潜伏期比较差异无统计学意义.结论 术中进行TceMEP监测,需避免盲目增加麻醉药物剂量加深麻醉;在脑电图未出现爆发-抑制波形时,使T4/T1维持在25%,可以有效记录TceMEP,又能降低患者发生体动的风险.

Abstract：

Objective To explore the influences of partial muscle relax and depth of anesthesia on transcranial electrical motor evoked potential (TceMEP).Methods 12 patients undergoing neurosurgical operation were enrolled.Anesthesia was maintained with sevoflurane , propofol and remifentanil.The level of muscle relax and anesthesia depth were monitored by train of five stimulation (TOF) and burst -suppressed rate (BSR).After the baseline recording when T4 equal tn T1 and there was no burst suppression wave on EEG( BSR =0), then BSR was increased to 0.25 ～0.5 and above 0.75 by regulating dosage of propofol and TceMEP was recorded respectively .At the state of disapperance of burst suppression wave and cisatracurium (40～ 80)μg/(kg/h) was administered simultaneously, when T4 / T1 was equal to 25% TceMEP was elicited again.The movements of patients were also assessed during monitoring.Results The incidence of patient's movement at baseline was high(9/10).At the state of recovery of muscle relax,movement incidence was decreased and the amplitude of TceMEP was attenuated greatly when 0.25 ＜ BSR ＜0.5 and BSR ＞0.75 comparing to baseline( ＜0.05 and ＜0.01 respectively).When BSR =0 and T4 /T1 was equal to 25% , a similar intensity stimulation could almost maintain the amplitude of TceMEP as well as baseline( P ＞0.05) ,but there was only 1 patient showing movement.The latency of TceMEPs was not significantly different comparing to baseline.Conclusions Monitoring of TceMEP need to avoid the presence of burst suppression waves EEG by deepening anaesthesia.TceMEP could be recorded at the state of partial muscle relax by T4 / T1 equal to 25% and without burst suppression wave EEG, in which the risk of movement of patients responsed to transcranial stimulation is decreased and the effect on TceMEP is reduced.     

Gustatory stimulation influences the processing of intranasal stimuli

OBJECTIVES: Taste and smell interact. The aim of this study was to examine this interaction using gustatory and olfactory stimuli applied at the same time, which exhibited perceptual compatibility and incompatibility. METHODS: Thirty-two, young, healthy normosmic subjects (16 men, 16 women) took part in two randomized sessions. Event-related potentials (ERP) were recorded in response to vanillin, or gaseous CO2. These two conditions were combined with three "taste conditions" including sweet taste, sour taste, and the intraoral presentation of an empty taste dispenser. RESULTS: Vanillin responses were largest for the "sweet" condition, while they were smaller for the "sour condition". In contrast, responses to CO2 were largest under the "sour" condition, and smallest under the "sweet" condition. Moreover, during the "sweet" condition the latencies of P1 and N1 were shorter than in the "sour" condition, which was the other way around for CO2. CONCLUSIONS: Results of the present investigation suggested that (1) the early processing of intranasal chemosensory stimuli is modulated through concomitant gustatory stimulation, and that (2) this modulation may depend, at least in part, on the contextual compatibility between intranasal and intraoral stimuli.     

度洛西汀和西酞普兰对抑郁症患者电刺激痛觉诱发电位P250的影响

目的 探讨不同药理机制的抗抑郁对抑郁症患者电刺激痛觉诱发电位P250的影响.方法 将60例不伴疼痛的抑郁症患者采用随机数字表法随机分为度洛西汀组(30例,口服度洛西汀60 mg/d)和西酞普兰组(30例,口服西酞普兰20～40 mg/d)治疗,并于治疗前、治疗第2周末测定电刺激痛觉诱发电位P250,与对照组(30名,正常健康人)进行比较;对度洛西汀组和西酞普兰组P250下降率与17项汉密尔顿抑郁量表(HAMD17)评分的相关性进行分析.结果 (1)度洛西汀组和西酞普兰组治疗前P250波幅分别为(36.4±6.8)、(35.2±6.5)μV,均高于对照组[(28.0±5.5)μV],差异有统计学意义(P均=0.000);3组P250潜伏期的差异无统计学意义(P=0.732).(2)度洛西汀组和西酞普兰组治疗第2周末P250波幅分别下降为(31.4±5.7)、(34.0±5.9)μV,均高于对照组,差异有统计学意义(P=0.020,P=0.000);2组治疗前后P250波幅的差异均有统计学意义(P=0.000,P=0.022),P250潜伏期的差异均无统计学意义(P=0.667,P=0.408).(3)度洛西汀组治疗第2周末P250波幅的下降值为(5.0±3.4)μV,下降率为(13±10)%,均高于西酞普兰组[(1.2±2.8)μV,(3±8)%],差异有统计学意义(P=0.000,P=0.000).(4)度洛西汀组和西酞普兰组治疗第2周末P250波幅下降率与HAMD17总分减分率无显著相关性(P=0.318,P=0.287),与焦虑/躯体化因子减分率呈正相关(分别r=0.370、P=0.034,r=0.417、P=0.009).结论 抗抑郁药对P250波幅有下调作用,并可独立于抗抑郁效应;度洛西汀的作用强于西酞普兰.

Abstract：

Objective To explore effects of antidepressants with distinct pharmacological property on electrical pain-related evoked potentials P250 in depression. Methods Sixty cases pain-free depressive inpatients were randomly divided into two groups, treated with duloxetine (60 mg/d, n = 30) or citalopram (20-40 mg/d, n = 30) respectively for 2 weeks. Pain-related evoked potentials P250 was measured before and after treatment, which was contrasted with healthy controls (n=30). Results The amplitudes of P250 were significandy higher in either duloxetine or citalopram group at baseline compared with controls [(36. 4 ±6.8), (35.2±6.5)μV vs. (28.0±5.5) μV , P = 0.000, P=0.000], and decreased significantly at the end of study [(31. 4 ± 5. 7) , (34. 0 ± 5. 9) μV, P =0. 000, P =0. 022 respectively]. Either the absolutely decreased value [(5.0 ±3. 4) μV vs. (1. 2 ±2. 8) μV, P =0.000] or the decreased ratio [(13±10)% vs.(3±8)%,P = 0. 000] of P250 amplitudes were significant higher in duloxetine group than citalopram group.The reduction of P250 amplitudes was not significantly related with the change of HAMD17 total score (P = 0. 318, P = 0. 287) , which was statistically positively correlate with the reduction rate of anxiety/somatization factor in either duloxetine group or citalopram group (r = 0. 370, P = 0. 034; r = 0. 417 , P =0. 009 respectively). Conclusion Duloxetine and citalopram possibly have down-regulating effects on P250 amplitude independent of antidepressant effects, with duloxetine being more effective than citalopram.     

Zonal expression and activity of glutathione S-transferase enzymes in the mouse olfactory mucosa

The rodent olfactory mucosa is characterized by a mosaic of gene expression that is exhibited among various cell types. Olfactory sensitivity in these animals is conveyed through odorant receptor families that are distinctly expressed within various subsets of the olfactory neuron population. Receptor neurons that express a particular class of odorant receptors exhibit bilaterally symmetric zones, which generally define their location within the nasal cavity. Less characterized are zonal expression profiles of proteins among non-neuronal cell types of the olfactory mucosa. In this study, we survey the expression of three glutathione S-transferase (GST) isozymes (alpha, mu, and pi) in the mouse olfactory mucosa and characterize the zonal expression of the mu isozyme. Immunohistochemistry and Western blot analysis of the GST mu isozyme reveal that the lateral olfactory turbinates I, Ib, II, IIb, and III display a greater intensity of expression for GST mu, in comparison to the dorsal and septal regions of the mucosa. GST alpha and pi isozymes do not display any distinct zonal organization in olfactory tissue of the adult mouse. When the general substrate 1-chloro-2-4-dinitrobenzene (CDNB) was used to assess GST activity within the olfactory tissue, the lateral turbinate regions displayed a higher level of activity when compared to dorsal or septal regions. Analysis of GST mu expression in prenatal and early postnatal olfactory tissue also reveals a zonal expression of the isozyme. We relate the significance of these findings to metabolic topography and olfactory chemosensory function.     

Effect of 17beta-estradiol on olfactory bulbectomy-induced oxidative stress and behavioral changes in rats

The present study evaluated 17beta-estradiol (17betaE(2)) (2.5 mg/kg sc) effects on bilateral OBX-induced behavioral changes and oxidative stress. OBX in male Wistar rats produced an increase in lipid peroxidation products and a decline in reduced glutathione (GSH) content and glutathione peroxidase (GSH-Px) activity, together with an increase in caspase-3 activity. Additionally, OBX triggered changes of behavior such as an enhancement of immobility time in the forced swim test and hyperactivity in the open field test. These changes were reversed by treatment with 17betaE(2) (14 days). Our results reveled that 17betaE(2) has a protective effect against oxidative stress, cell damage and behavioral changes induced by OBX, and present antidepressant and antianxiety properties.     

Odor-induced metabolic activity in the olfactory bulb of rats trained to detect propionic acid vapor

The pattern of glucose metabolism in the glomerular layer of the main olfactory bulb was studied in rats trained to sample brief odor stimuli. After injection with [¹⁴C]2-deoxyglucose (2-DG), 5 rats were tested for discrimination of propionic acid from air. Over the 45 min test period rats sampled the stimulus for 0.5–0.8 s during each trial and their total exposure to the stimulus was 53–147 s. A discrete focus of increased glucose metabolism was found in the central dorsomedial sector of the glomerular layer in each animal. The position of this focus and the overall pattern of glomerular layer activity was essentially identical to that obtained in 4 control rats which were exposed passively to alternating 5 min periods of the odor and clean air for 45 min. The size of the primary focus was only slightly smaller in the trained rats, despite the large difference in total exposure time. The absence of olfactory adaptation during the behavioral tests and the similar pattern of 2-DG uptake in controls and trained animals indicate that adaptation does not play a significant role in the patterns of glucose metabolism induced in the glomeruli of the olfactory bulb by extended exposure to an odor.     

Quantitative analysis of the olfactory pathway for drug delivery to the brain

Following intranasal administration to rats, wheat germ agglutinin-horseradish peroxidase (WGA-HRP) concentrated in the olfactory nerve and glomerular layers of the olfactory bulb resulting in a mean olfactory bulb concentration of 140 nM. A negligible amount of label was detected in the olfactory bulb following intravenous administration of WGA-HRP or intranasal administration of unconjugated HRP. This is the first quantitative assessment of intraneuronal transport of a protein into the brain using the olfactory route.     

Effects of dopamine and norepinephrine on neuronal activity of the olfactory tubercle

The effects of iontophoretic administration of norepinephrine (NE) and dopamine (DA) on olfactory tubercle (OT) neurons that respond to lateral hypothalamus (LH) or locus coeruleus (LC) electrical stimulation were studied. NE and DA decreased the frequency of OT neurons which were increased or decreased by the LH stimulation. An increased firing of OT neurons following NE or DA administration was less frequently observed. NE administration decreased the firing of OT neurons that responded to LC stimulation. These results suggest that the LC fibers which reach the OT use NE as a neurotransmitter. DA administration also suppressed the unitary discharge of OT neurons responding to LC stimulation. The increase in frequency of OT neurons observed following LH stimulation cannot be attributed to DA. The possibility that other suspected neural transmitters are involved in this effect is discussed.     

the connections of the mouse olfactory bulb: A study using orthograde and retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase

The efferent and centrifugal afferent connections of the main olfactory bulb (MOB) of the mouse were studied by orthograde and retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). MOB projects ipsilaterally to the anterior olfactory nucleus, taenia tecta, anterior hippocampal continuation, indusium grisium, olfactory tubercle, and the lateral and medial divisions of the entorhinal area. In the region of the anterior one-half to two-thirds of the posterior division of the insular cortex the projection from MOB extends into the insular cortex. The only efferent projection of MOB to the contralateral half of the brain was to the anterior olfactory nucleus. All efferent projections of MOB, thus, are to telencephalic structures. By contrast the centrifugal afferents to MOB originate from every major division of the neuraxis. Neurons projecting to the bulb were found ipsilaterally in all divisions of the anterior olfactory nucleus (AON). In some cases, labeling in the external division of AON was weak or absent. In the contralateral AON, pars externa was the most intensively labeled sub-division. Retrogradely labeled neurons were also present in all other subdivisions of the contralateral AON but were fewer in number and less heavily labeled than in the ipsilateral AON. Ipsilaterally, positive neurons were also present in taenia tecta, and the anterior hippocampal continuation. There was profuse retrograde labeling of neurons in the entire extent of the ipsilateral piriform cortex (PC). There was a rostral to caudal gradient of labeling in PC with more positive neurons in rostral than caudal parts. Labeled neurons were present in the lateral entorhinal cortex LEC and in the transitional cortex between LEC and PC. Very heavy retrograde labeling was present in the nuclei of the horizontal and vertical limbs of the diagonal band (HDB and VDB). More cells were labeled in HDB than in VDB. Neurons were labeled in the ipsilateral nucleus of the lateral olfactory tract (NLOT) and, when the injection spread into the accessory olfactory bulb, labeled neurons were present ventral to NLOT in accessory NLOT. A few lightly labeled neurons were always present in the posterolateral and medial cortical amygdaloid areas. Neurons were labeled in the zona inserta and scattered throughout several hypothalamic nuclei. There was massive retrograde labeling of neurons in the locus coeruleus and neurons were abundantly labeled in the dorsal and medial raphe nuclei and nucleus raphe pontis. In general, the labeling of MOB connections was more extensive than that which has been reported in closely related species.(ABSTRACT TRUNCATED AT 400 WORDS)