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PubMed2006

Unilateral low-frequency stimulation of central piriform cortex delays seizure development induced by amygdaloid kindling in rats.

Low-frequency stimulation of the kindling site interferes with the course of kindling epileptogenesis. The present study examined the effect of unilateral low-frequency stimulation of the central piriform cortex on seizure development induced by amygdaloid kindling in rats. The ipsilateral or contralateral central piriform cortex received low-frequency stimulation (15 min train of 0.1 ms pulses at 1 Hz and 50-150 muA) immediately after termination of once daily kindling stimulation (2 s train of 1 ms pulses at 60 Hz and 150-300 microA) in the right amygdala for 30 days. Low-frequency stimulation of either the ipsilateral or contralateral central piriform cortex significantly suppressed the progression of seizure stages and reduced afterdischarge duration throughout the course of amygdaloid kindling. The marked suppression induced by low-frequency stimulation of the central piriform cortex on either side was predominantly due to the significant retardation of progression from stage 0 to stage 1 and stage 3 to stage 4 seizures. In addition, the suppressive effect of low-frequency stimulation did not disappear when the stimulation was stopped; it could persist for at least 10 days. These findings indicate that brain areas other than the kindling focus, such as the central piriform cortex on both sides, can also be used as reasonable targets for low-frequency stimulation to retard seizure development induced by amygdaloid kindling. Secondly, like the ipsilateral central piriform cortex, the contralateral central piriform cortex may also participate in the progression and secondary generalization of focal seizures. The study suggests that unilateral low-frequency stimulation of the central piriform cortex may have a significant antiepileptogenic effect, and may be helpful for exploring effective and long-lasting therapies for human temporal lobe epilepsy.

Amygdala↗
PubMed2006

The magnocellular medial preoptic nucleus I. Sources of afferent input.

The magnocellular medial preoptic nucleus plays a crucial role in the regulation of male sexual behavior in Syrian hamsters. Histological and behavioral studies suggest that the magnocellular medial preoptic nucleus regulates male mating behavior by integrating chemosensory and hormonal signals. The present study is the first to systematically identify the afferent connections of the magnocellular medial preoptic nucleus by tracing the uptake of cholera toxin B from deposits in the magnocellular medial preoptic nucleus of adult male Syrian hamsters. Our findings indicate that the magnocellular medial preoptic nucleus receives 1) chemosensory input from areas in the main and accessory olfactory pathways including the posterior medial bed nucleus of the stria terminalis, anterior medial, anterior cortical and posterior cortical nuclei of the amygdala; 2) input from steroid responsive structures such as the posterior medial nucleus of the amygdala, bed nucleus of the stria terminalis, lateral septum, anteroventral periventricular nucleus, medial preoptic nucleus, ventromedial nucleus of the hypothalamus and arcuate nucleus; 3) input from structures in the brainstem such as the subparafascicular thalamic nucleus, peripeduncular nucleus and the premamillary nucleus in the hypothalamus that carry sensory information from the genitalia. The major afferent input to the magnocellular medial preoptic nucleus was confirmed by injecting anterograde tracer biotinylated dextran amine into the anterior medical nucleus of the amygdala, the posterodorsal part of the medial nucleus of the amygdala, the posteromedial part of the bed nucleus of the stria terminalis and the posterointermediate part of the bed nucleus of the stria terminalis. Our results support the hypothesis that the magnocellular medial preoptic nucleus is part of the chemosensory pathway that receives chemosensory and hormonal input to regulate mating behavior and suggest that the magnocellular medial preoptic nucleus may utilize information from the genitalia to regulate male mating behavior.

Afferent Pathways↗
PubMed2006

Synaptic adaptation and odor-background segmentation.

Habituation is a form of non-associative memory that plays an important role in filtering stable or redundant inputs. The present study examines the contribution of habituation and cortical adaptation to odor-background segmentation. Segmentation of target odorants from background odorants is a fundamental computational requirement for the olfactory system. Recent electrophysiological data have shown that odor specific adaptation in piriform cortex neurons, mediated at least partially by synaptic adaptation between the olfactory bulb outputs and piriform cortex pyramidal cells, may provide an ideal mechanism for odor-background segmentation. This rapid synaptic adaptation acts as a filter to enhance cortical responsiveness to changing stimuli, while reducing responsiveness to static, potentially background stimuli. Using previously developed computational models of the olfactory system, we here show how synaptic adaptation at the olfactory bulb input to the piriform cortex, as demonstrated electrophysiologically, creates odor specific adaptation. We show how this known feature of olfactory cortical processing can contribute to adaptation to a background odor and to odor-background segmentation. We then show in a behavioral experiment that the odor-background segmentation is perceptually important and functions at the same time-scale as the synaptic adaptation observed between the olfactory bulb and cortex.

Adaptation, Physiological↗
PubMed2005

Unpleasant odors increase pain processing in a patient with neuropathic pain: psychophysical and fMRI investigation.

A 49-year old man with neuropathic pain in his right elbow, wrist and digits III-V of his hand reported that certain odors increased his pain by superimposing an electric shock-like pain to his already existing pain. Psychophysical testing revealed that the best predictor of pain exacerbation was odor unpleasantness. Functional magnetic resonance imaging (fMRI) showed increased activation following an unpleasant odor in pain related areas, including the thalamus, amygdala, insular and anterior cingulate cortices, with similar trends in primary somatosensory cortex hand/arm area. The increased pain and associated neural activations in response to unpleasant odors may be related to the phenomenon of synesthesia, to a rewiring of olfactory pathways onto pain pathways mimicking synesthesia or, to activation of the sympathetic nervous system.

Arm↗
PubMed2006

Wiring specificity in the olfactory system.

The fruitfly brain learns about the olfactory world by reading the activity of about 50 distinct channels of incoming information. The receptor neurons that compose each channel have their own distinctive odour response profile governed by a specific receptor molecule. These receptor neurons form highly specific connections in the first olfactory relay of the fly brain, each synapsing with specific second order partner neurons. We use this system to discuss the logic of wiring specificity in the brain and to review the cellular and molecular mechanisms that allow such precise wiring to develop.

Animals↗
PubMed2006

Formation of glomerular maps in the olfactory system.

Sensory perception relies on the decoding of external stimuli into an internal neuronal representation, which requires precise connections between the periphery and the brain. In the olfactory system the axons of chemosensory neurons with the same odorant receptor coalesce into common glomeruli in the olfactory bulb, forming a receptor-topic map. The creation of this map begins prenatally when axons navigate towards the bulb, resort in a receptor-specific manner and terminate in a broad area interdigitated with other axon populations; distinct glomeruli form postnatally. While the initial process of glomerulization requires mainly molecular determinants, activity-dependent processes lead to a refinement of glomerular organization.

Animals↗
PubMed2005

The anatomical logic of smell.

Olfactory receptor neurons (ORNs) expressing the same odorant receptor gene share ligand-receptor affinity profiles and converge onto common glomerular targets in the brain. The activation patterns of different ORN populations, evoked by differential binding of odorant molecular moieties, constitute the primary odor representation. However, odorants possess properties other than receptor-binding sites that can contribute to odorant discrimination. Among terrestrial vertebrates, odorant sorptiveness--volatility and water solubility--imposes physicochemical constraints on migration through the nose during inspiration. The non-uniform distributions of ORN populations along the inspiratory axis enable sorptiveness to modify odor representations by affecting the number of molecules reaching different receptors during a sniff. Animals can then modify and analyze odor representation further by the dynamic regulation of sniffing.

Animals↗
PubMed2007

Spatiotemporal representations in the olfactory system.

A complete understanding of the mechanisms underlying any kind of sensory, motor or cognitive task requires analysis from the systems to the cellular level. In olfaction, new behavioural evidence in rodents has provided temporal limits on neural processing times that correspond to less than 150ms--the timescale of a single sniff. Recent in vivo data from the olfactory bulb indicate that, within each sniff, odour representation is not only spatially organized, but also temporally structured by odour-specific patterns of onset latencies. Thus, we propose that the spatial representation of odour is not a static one, but rather evolves across a sniff, whereby for difficult discriminations of similar odours, it is necessary for the olfactory system to "wait" for later-activated components. Based on such evidence, we have devised a working model to assess further the relevance of such spatiotemporal processes in odour representation.

Animals↗
PubMed1998

Illness from low levels of environmental chemicals: relevance to chronic fatigue syndrome and fibromyalgia.

This article summarizes (1) epidemiologic and clinical data on the symptoms of maladies in association with low-level chemicals in the environment, i.e., environmental chemical intolerance (CI), as it may relate to chronic fatigue syndrome (CFS) and fibromyalgia; and (2) the olfactory-limbic neural sensitization model for CI, a neurobehavioral synthesis of basic and clinical research. Severe CI is a characteristic of 20-47% of individuals with apparent CFS and/or fibromyalgia, all patients with multiple chemical sensitivity (MCS), and approximately 4-6% of the general population. In the general population, 15-30% report at least minor problems with CI. The levels of chemicals reported to trigger CI would normally be considered nontoxic or subtoxic. However, host factors--e.g., individual differences in susceptibility to neurohormonal sensitization (amplification) of endogenous responses--may contribute to generating a disabling intensity to the resultant multisystem dysfunctions in CI. One site for this amplification may be the limbic system of the brain, which receives input from the olfactory pathways and sends efferents to the hypothalamus and the mesolimbic dopaminergic [reward] pathway. Chemical, biologic, and psychological stimuli can initiate and elicit sensitization. In turn, subsequent activation of the sensitized limbic and mesolimbic pathways can then facilitate dysregulation of behavioral, autonomic, endocrine, and immune system functions. Research to date has demonstrated the initiation of neurobehavioral sensitization by volatile organic compounds and pesticides in animals, as well as sensitizability of cardiovascular parameters, beta-endorphin levels, resting EEG alpha-wave activity, and divided-attention task performance in persons with CI. The ability of multiple types of widely divergent stimuli to initiate and elicit sensitization offers a new perspective on the search for mechanisms of illness in CFS and fibromyalgia with CI.

Controlled Clinical Trials as Topic↗
PubMed2001

Predicted profiles of ion concentrations in olfactory cilia in the steady state.

The role of ciliary geometry for transduction events was explored by numerical simulation. The changes in intraciliary ion concentrations, suspected to occur during transduction, could thus be estimated. The case of a single excised cilium, having a uniform distribution of membrane channels, voltage clamped to -80 mV, was especially investigated. The axial profile of membrane voltage was that of a leaky cable. The Ca(2+) concentration profile tended to show a maximum in proximal segments, due to a preponderance of Ca(2+) inflow over Ca(2+) export at those locations. The local increase in Ca(2+) concentration activated Cl(-) channels. The resulting current caused a local drop in Cl(-) concentration, especially at the tip of the cilium and in distal segments, accompanied by a drop in ciliary K(+) concentration. In consequence, the membrane Cl(-) current was low in distal segments but stronger in proximal segments, where resupply was sufficient. The model predicts that the Cl(-) depletion will codetermine the time course of the receptor potential or current and the ciliary stimulus-response curve. In conclusion, when modeling with transduction elements presently known to participate, the ciliary geometry has large effects on ion distributions and transduction currents because ciliary ion transport is limited by axial electrodiffusion.

Animals↗
PubMed2003

The olfactory responses of the antenna and maxillary palp of the fleshfly, Neobellieria bullata (Diptera: Sarcophagidae), and their sensitivity to blockage of nitric oxide synthase.

The relative sensitivities of the olfactory receptors in the antenna and maxillary palp of the fleshfly, Neobellieria bullata, were assessed using simultaneous electroantennograms (EAGs) and electropalpograms (EPGs). In general, the antennae and maxillary palps were more sensitive to odors related to animals (blood extract and saturated carboxylic acid) than to odors that were plant-derived (citral, hexenol, hexenal). In addition, the maxillary palps were relatively less sensitive to plant-derived odorants than the antennae, perhaps related to their anatomical position. Scanning electron microscopy was also used to assess the types of sensilla found on the two organs. In addition, NADPH-diaphorase histochemistry was used in an attempt to localize the enzyme nitric oxide synthase (NOS) in the antenna and the maxillary palps. We found evidence of NADPH-diaphorase staining in both organs, with localized staining in the antennal cells and more general staining in the maxillary palps. When NOS was selectively blocked using the antagonist L-NAME, the amplitude of the EAGs and EPGs to odorants fell by 30-50%. In contrast, application of the inactive enantiomer, D-NAME, did not change the amplitude of the EAGs or the EPGs. Our results indicate that NOS is involved in the function of olfactory receptor cells in the fleshfly.

Animals↗
PubMed1998

Physiology and morphology of olfactory neurons associating with the protocerebral lobe of the honeybee brain.

Physiology and morphology of olfactory neurons associated with the protocerebral lobe around the alpha-lobe of the mushroom body were studied in the brain of the honeybee Apis mellifera using intracellular recording and staining techniques. The responses of neurons to behaviorally relevant odorants (a blend, and components of the Nasonov pheromone, and some other non-pheromonal odors) were recorded. Different response patterns were observed within different neurons, and often within the same neuron, in response to different stimuli. All the neurons stained had innervations in the protocerebral lobe. The cell profiles varied from cells connecting the antennal lobe with both the protocerebral and lateral protocerebral lobes (projection neurons), cells linking the pedunculus of the mushroom body with both the protocerebral and lateral protocerebral lobes (PE1 neurons), cells linking the alpha-lobe and protocerebral lobe with the calyces of the mushroom body (feedback neurons), and cells linking the alpha-lobe and protocerebral lobe with the antennal lobe (recurrent neurons), to cells connecting the protocerebral lobe with the contralateral protocerebrum (bilateral neurons). These findings suggest that the protocerebral lobe acts as an olfactory center associating with other centers, and provides multi-layered recurrent networks within the protocerebrum and between the deutocerebrum and the protocerebrum in honeybee olfactory pathways.

Journal Article↗
PubMedDate not supplied

Neuroendocrine control of urine-marking behavior in male rats.

Sexually experienced Wistar male rats were used to investigate (a) urine voiding in the presence of nearby estrous females and the control of such voiding by (b) steroid hormones and (c) peripheral nerves supplying the genitourinary system. The first experiment showed that males always have a low rate of urine voiding that is significantly increased when a receptive female is around. Thus, it is suggested that an airborne scent from the female stimulates the olfactory system of males, triggering urine emission to transmit sex-related messages, i.e., male rats display the well-known urine-marking behavior of mammals. The number of urine marks and sniffing to females decreased after castration, and were restored after exogenous treatment with testosterone or estradiol. The proposed hypothesis is that airborne scents from the female activate the aromatization process in nuclei of the olfactory pathway of the male, evoking a cascade of neuronal responses that finish in urine marking. Peripheral nerves supplying the genitourinary system are the viscerocutaneous branch of the pelvic nerve (Vc) and the hypogastric (Hg). Data showed that both nerves are important for the central control of urine storage and voiding. Transection of Vc almost blocked urine marking, while Hg lesion increased the number of marks. Thus, it is discussed that Vc is the most important nerve in charge of voiding the bladder, and that Hg is important for continence.

Animals↗
PubMed1997

Deafferentation of the olfactory bulbs of male rats reduces erection to remote cues from females.

If male rats are paired with a receptive, soliciting female rat in a setting that prevents physical contact, but permits auditory, visual, and olfactory contact, some will have erections of the penis--noncontact erections (NCE). Surgical deafferentation of the olfactory bulbs from all the known chemosensory systems of the nasal septum renders rats anosmic, decreases sexual performance in copulation tests with females, and substantially reduces the frequency of NCE. Thus, NCE appear to be primarily regulated though the olfactory perception of volatile chemosensory cues from receptive females.

Animals↗
PubMed1998

Odorant receptors govern the formation of a precise topographic map.

Olfactory neurons expressing a given odorant receptor project with precision to 2 of the 1800 glomeruli within the olfactory bulb to create a topographic map of odor quality. We demonstrate that deletions or nonsense mutations in the P2 odorant receptor gene cause the axons of these cells to wander rather than converge on a specific glomerulus. Receptor substitution experiments that replace the P2 gene with the coding region of the P3 gene result in the projection of P3-->P2 axons to a glomerulus touching the wild-type P3 glomerulus. These data, along with additional receptor substitutions, indicate that the odorant receptor plays an instructive role in the establishment of the topographic map.

Animals↗
PubMed2002

Representation of the glomerular olfactory map in the Drosophila brain.

We explored how the odor map in the Drosophila antennal lobe is represented in higher olfactory centers, the mushroom body and lateral horn. Systematic single-cell tracing of projection neurons (PNs) that send dendrites to specific glomeruli in the antennal lobe revealed their stereotypical axon branching patterns and terminal fields in the lateral horn. PNs with similar axon terminal fields tend to receive input from neighboring glomeruli. The glomerular classes of individual PNs could be accurately predicted based solely on their axon projection patterns. The sum of these patterns defines an "axon map" in higher olfactory centers reflecting which olfactory receptors provide input. This map is characterized by spatial convergence and divergence of PN axons, allowing integration of olfactory information.

Algorithms↗
PubMed2002

Spatial representation of the glomerular map in the Drosophila protocerebrum.

In the fruit fly, Drosophila, olfactory sensory neurons expressing a given receptor project to spatially invariant loci in the antennal lobe to create a topographic map of receptor activation. We have asked how the map in the antennal lobe is represented in higher sensory centers in the brain. Random labeling of individual projection neurons using the FLP-out technique reveals that projection neurons that innervate the same glomerulus exhibit strikingly similar axonal topography, whereas neurons from different glomeruli display very different patterns of projection in the protocerebrum. These results demonstrate that a topographic map of olfactory information is retained in higher brain centers, but the character of the map differs from that of the antennal lobe, affording an opportunity for integration of olfactory sensory input.

Animal Structures↗