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Sex pheromone systems in goldfish: comparisons to vomeronasal systems in tetrapods.

Most amphibians, reptiles and mammals possess a well defined dual olfactory system comprised of separate neural pathways that regulate different olfactory functions. One pathway originates in the nasal cavity and gives rise to what is commonly referred to as the main olfactory system. The other pathway originates in the vomeronasal organ (VNO) and gives rise to the accessory olfactory system. Functionally, the main olfactory system is thought to subserve, olfactory-mediated tasks such as feeding and grooming, while the accessory olfactory system is believed to be primarily involved in mediating behavioral and physiological responses to sex pheromones. Traditionally, it has been difficult to address whether teleosts possess any components of the vomeronasal system, since they generally do not meet the criteria used to identify vomeronasal systems in other vertebrates. Previous conclusions that the nasal epithelia of fish is olfactory and not vomeronasal in nature are based on observations that teleosts lack a separate VNO-like chemosensory structure and an anatomically distinct accessory olfactory bulb. However, because sex pheromones have been identified in the goldfish, it is now possible to compare the neural substrates that regulate pheromone-induced responses in teleosts to those that mediate similar responses in other vertebrates. The olfactory system in goldfish is particularly well suited for such comparisons, because it comprises anatomical and functional subdivisions that resemble those associated with the main and accessory olfactory systems in tetrapods. The olfactory pathways that mediate endocrine and behavioral responses to sex pheromones in goldfish are described and then compared to the main and accessory olfactory systems of tetrapods. In making these comparisons, a number of similarities become apparent. First, the olfactory pathways that regulate responses to sex pheromones in goldfish are different from those that serve a more general olfactory function. Second, these functional differences appear to be subserved by separate and anatomically distinct olfactory tract projections to the brain. Third, the lateral olfactory tracts and their central projections in goldfish appear to serve a function analogous to that of the main olfactory system, while the medial olfactory tracts and their central projections comprise a pathway remarkably similar to the vomeronasal-accessory olfactory system. These findings suggest that teleosts may possess functional correlates of tetrapod vomeronasal systems, but in a form that has yet to be recognized. If so, medial olfactory tract projections in goldfish may be evolutionarily conserved and expressed in tetrapods as the vomeronasal system, or the medial olfactory tract projections may be new pathways that have evolved to serve the same function.

Animals↗

Developmental changes in olfactory bulb projections revealed by degeneration argyrophilia.

The maturation of the main and accessory olfactory bulb projections to the ventral forebrain of the golden hamster has been traced by using the Fink-Heimer silver technique to stain degenerating axons and terminal arborizations after bulbectomy at different ages between birth and 33 days. In the youngest pups, long-lasting degeneration argyrophilia (LLDA) is found in two regions of prepiriform cortex: at the level of the rostral tubercle and rostral amygdala. By five days of age the caudal region exhibiting a long-lasting degeneration reaction extends from the middle of the olfactory tubercle to the middle of the amygdala. The olfactory tubercle, medial and cortical amygdala and entorhinal cortex subsequently develop substantial LLDA at ages varying between 9 and 13 days. In a previous study (Leonard, '74b) the onset of LLDA in optic tract terminals in the superior colliculus was found to coincide with the age of eye opening and the onset of a stage of rapid snyapse formation. Since different olfactory responses appear at different times during the golden hamster pup's first two weeks of postnatal life, it seems possible that the onset of LLDA in different regions of the olfactory projection at different ages may be related to the onset of different specific olfactory functions.

Amygdala↗

The potion's magic.

During remembering, a perception of the past is constructed that includes sensory details of the original episode. In this issue of Neuron, Gottfried and colleagues provide evidence for selective piriform activation during recognition of visual cues previously paired with scents. These data provide evidence of sensory-specific reactivation of olfactory cortex during remembering.

Auditory Cortex↗

OCAM reveals segregated mitral/tufted cell pathways in developing accessory olfactory bulb.

Two functional subsets of vomeronasal sensory neurons project their axons to two segregated zones in the accessory olfactory bulb (AOB). Using immunohistochemical methods with antibodies against the novel cell adhesion molecule OCAM, we provide evidence that the segregation of functional pathways is maintained at the level of mitral/tufted (M/T) cells of the mouse AOB and that this pattern emerges early in ontogeny. During embryonic and postnatal development OCAM was strongly expressed by M/T cells in the caudal zone of the AOB where OCAM-negative vomeronasal axons terminated. In contrast, rostral zone M/T cells innervated by OCAM-positive vomeronasal axons displayed no or faint OCAM immunoreactivity. Differential expression of OCAM in segregated M/T cell pathways suggests that OCAM may be involved in defining compartments of connectivity and setting up functional subdivisions in the developing AOB.

Aging↗

CCK-A and CCK-B receptors enhance olfactory recognition via distinct neuronal pathways.

We have previously reported that CCK-A receptor agonists and CCK-B receptor antagonists both enhance memory in an olfactory recognition test. Here, we report that the memory-enhancing effect of the CCK-B receptor antagonist L-365,260 (1 mg/kg i.p.), but not that of the CCK-A receptor agonist caerulein (0.03 mg/kg i.p.), was dramatically decreased following a bilateral transection of the perforant path, a principal source of input to the hippocampal formation. We further confirmed that a significant memory deficit occurred subsequent to this deafferentation of the hippocampus in untreated animals. In contrast, the effect of caerulein, but not that of L-365,260, was abolished following a bilateral subdiaphragmatic vagotomy. These results demonstrate that the hippocampal system plays a role in olfactory recognition and indicate that distinct neuronal pathways underlie the memory-enhancing effects of CCK-A and CCK-B drugs observed in the olfactory recognition test. The former effects (CCK-A) appear to involve a peripheral relay to the brain via the vagus nerve, whereas the latter (CCK-B) are directly central and involve, at least in part, the hippocampal system.

Animals↗

The efferent connections of the suprachiasmatic nucleus of the hypothalamus.

The efferent connections of the suprachiasmatic nucleus of the hypothalamus have been studied in the rat by the injection of 3H-proline into the nucleus and the surrounding regions of the rostral hypothalamus, and by the injection of the enzyme marker, horseradish peroxidase, into the region of the ventromedial hypothalamic nucleus. After an injection of 3H-proline confined to the ventral portion of the suprachiasmatic nucleus, transported label can be followed, in the autoradiographs, dorsally and caudally in the periventricular area as far as the caudal end of the ventromedial nucleus, into the triangular area between this nucleus and the arcuate nucleus, and along the ventral aspect of the tuberal region, just lateral to the ventromedial nucleus. A small number of silver grains are also seen over the internal lamina of the median eminence. No label can be followed rostrally or immediately lateral to the nucleus. Comparable injections into adjoining regions of the hypothalamus (especially the anterior hypothalamic area, the medial preoptic area, and the retrochiasmatic region) show transported label over the same regions, but with a somewhat different pattern of grain distribution; in addition, the anterior hypothalamic area shows an extensive projection through the medial forebrain bundle to the mammillary and supramammillary nuclei, the midbrain tegmentum, and certain of the midline thalamic nuclei. Although it is difficult in our autoradiographs to distinguish between the course of the efferent fibers from the suprachiasmatic nucleus and the zones in which they terminate, our evidence favors a termination among the cells of the periventricular area, and upon dendrites of the cells in the ventromedial, dorsomedial and arcuate nuclei, which extend beyond the limits of the nuclei into the periventricular area and to the area beneath the ventromedial nucleus.

Amygdala↗

Encoding of novel picture pairs activates the perirhinal cortex: an fMRI study.

It is well established in nonhuman primates that the medial temporal lobe (MTL) structures, the hippocampus and the entorhinal and perirhinal cortices, are necessary for declarative memory encoding. In humans, the neuropathological and neuropsychological changes in early Alzheimer's disease (AD) further support a role for the rhinal cortex in the consolidation of new events into long-term memory. Little is known, however, regarding the function of the rhinal cortex in humans in vivo. To examine the participation of the interconnected MTL structures as well as the whole-brain network of activated brain areas in visual associative long-term memory, functional magnetic resonance imaging (fMRI) was used to determine the brain regions that are activated during encoding and retrieval of paired pictures in 12 young control subjects. The most striking finding in the MTL activation pattern was the consistent activation of the perirhinal cortex in the encoding-baseline and encoding-retrieval comparisons with a strict statistical threshold (P < 0.00001). In contrast, no perirhinal cortex activation was detected in the retrieval-baseline or retrieval-encoding comparisons even with a low statistical threshold (P < 0.05). The location of the perirhinal activation area was in the transentorhinal part of the perirhinal cortex, in the medial bank of the collateral sulcus. The hippocampus and the more posterior parahippocampal gyrus were activated in both encoding and retrieval conditions. During the encoding processing, MTL activations were more consistent and the hippocampal activation area located more anteriorly than during retrieval. The frontal, parietal, temporal, and occipital association cortices were also activated in the encoding-baseline and retrieval-baseline comparisons. The data suggest that encoding, but not retrieval, of novel picture pairs activates the perirhinal cortex. To our knowledge, this is the first fMRI study reporting encoding activation in this transentorhinal part of the perirhinal cortex, the site of the very earliest neuropathological changes in AD.

Adult↗

Some connections of the entorhinal (area 28) and perirhinal (area 35) cortices of the rhesus monkey. II. Frontal lobe afferents.

In this investigation, the efferent cortico-cortical projections of the orbitofrontal cortex in the rhesus monkey have been investigated using silver impregnation methods. Projections from this area were observed to terminate in the rostral portions of the temporal lobe (areas TA, TE and TG) and cingulate gyrus (area 24), the insular cortex, and some dorsolateral prefrontal areas. Although these connections characterized all areas, with the exception of Walker's area 14 and Bonin and Bailey's area FL, the caudal levels of the orbitofrontal area were found to give rise to an additional projection which terminated in the entorhinal cortex and the transitional cortices bordering the rhinal sulcus. The source of this projection correlated closely with an area labeled FF by Bonin and Bailey. This connection may provide a much more direct means for the frontal lobe to influence the hippocampus than those involving the cingulate gyrus.

Amygdala↗

Feedback loops link odor and pheromone signaling with reproduction.

Pheromones can have profound effects on reproductive physiology and behavior in mammals. To investigate the neural circuits underlying these effects, we used a genetic transneuronal tracer to identify neurons that synapse with GnRH (LHRH) neurons, the key regulators of reproduction. We then asked whether the connected neurons are presynaptic or postsynaptic to GnRH neurons and analyzed their responses to chemosensory cues. Surprisingly, these experiments indicate that GnRH neurons receive pheromone signals from both odor and pheromone relays in the brain and may also receive common odor signals. Moreover, feedback loops are evident whereby GnRH neurons could influence both odor and pheromone processing. Remarkably, approximately 800 GnRH neurons communicate with approximately 50,000 neurons in 53 functionally diverse brain areas, with some connections exhibiting sexual dimorphism. These studies reveal a complex interplay between reproduction and other functions in which GnRH neurons appear to integrate information from multiple sources and modulate a variety of brain functions.

Amygdala↗

Orthonasal and retronasal odorant identification based upon vapor phase input from common substances.

Subjects were trained to identify by assigned number common substances presented as vapor phase stimuli via an orthonasal or a retronasal route. Following training, odorant identification learning was evaluated by measuring ability to correctly identify to a criterion. Those who met the criterion were then tested first with the stimuli presented to the nares that differed in location from the nares used in training, and second to the nares that corresponded in location to the nares used in training. It was found that, under conditions of natural retronasal breathing, orthonasally trained subjects made correct identifications on approximately 80% of the trials upon retronasal testing, but for the following orthonasal testing identifications were significantly more frequent, approaching 100% correct. After subsequent retronasal training, the same subjects' orthonasal identifications remained significantly higher, although identifications improved to approximately 92% correct on retronasal trials. Other subjects were instructed in a breathing technique designed to enhance retronasal stimulation. After orthonasal training, retronasal testing of these subjects still gave significantly fewer correct identifications than orthonasal testing, notwithstanding the modified retronasal breathing, but after subsequent retronasal training correct identifications by these subjects no longer differed significantly between orthonasal and retronasal testing. Efficacy of modified retronasal breathing was confirmed in two subsequent experiments. The observed substantial positive transfers between retronasal and orthonasal odorant identification training and testing loci demonstrate that these odorant pathways do not subserve completely independent olfactory systems, while the less accurate identifications via the retronasal route, unless instruction in retronasal breathing was given, suggest a difference in the efficiency with which odorants are normally delivered to the olfactory mucosa.

Adolescent↗

Neuropathology of spasmodic dysphonia.

Spasmodic dysphonia is a devastating voice disorder of unknown etiology, with a variable clinical presentation and response to treatment. Three independent evaluations of brain stem function were performed on spasmodic dysphonic patients, and age and sex-matched controls. Statistically significant (p less than 0.01 approximately 0.05) differences were noted between these groups, and the findings were consistent with impairment of somatic and visceral brain stem pathways. A significant correlation (p less than 0.05) was found between the severity of tested central nervous system impairment and vocal tremor, number of associated neurologic signs and duration of illness. Possible etiologies (viral or traumatic), age, and sex, did not correlate with the severity of brain stem impairment. Clinical signs and the brain stem findings appeared to stabilize 3 to 5 years after onset of dysphonia. The investigation of other spasmodic cranial nerve disorders afforded insight into the etiology and therapy for spasmodic dysphonia. Drawing upon previous observations and the results of the brain stem tests, two models are proposed for neuronal processing in spasmodic dysphonia, and future strategies are discussed. The evidence cited in this research project are consistent with spasmodic dysphonia being one of several spasmodic brain stem disorders with variable presentation which are known by the cranial nerve nuclei or pathways of major clinical involvement.

Adult↗

The differential projections of the olfactory bulb and accessory olfactory bulb in mammals.

Three species were studied, the rabbit, opossum and rat. Lesions of the main olfactory bulb caused terminal degeneration, assayed by the Fink-Heimer method, to occur in the ipsilateral olfactory tubercle, prepyriform cortex (including its periamygdaloid part), ventrolateral entorhinal area, and in anterior and posterolateral divisions of the cortical amygdaloid nucleus. The various parts of the ipsilateral anterior olfactory nucleus and the rostroventral end of the anterior continuation of the hippocampus (hippocampal rudiment) also received this projection. Lesions of the accessory olfactory bulb, which receives its sensory input from the vomeronasal (Jacobson's) organ, caused terminal degeneration to occur in the medial amygdaloid nucleus and in a posteromedial part of the cortical amygdaloid nucleus. This projection was conveyed by an accessory olfactory tract, which is accompanied in part of its course by a small nucleus, the bed nucleus of the accessory olfactory tract. The accessory olfactory tract is initially a part of the lateral olfactory tract but becomes increasingly indivuated at more posterior levels. It parts company with the lateral olfactory tract at the rostral end of the amygdaloid region, and, in addition to distributing to the medio-cortical amygdaloid region, it enters the stria terminalis to terminate in the bed nucleus of the stria terminalis in a small region bearing cytoarchitectonic resemblance to the medial amygdaloid nucleus. The topographic segregation of the areas of termination of the olfactory and accessory olfactory (vomeronasal) projections is suggestive of a functional dichotomy in the organization of the olfactory system...

Amygdala↗