Chemical Identification of "Maternal Signature Odors" in Rat.

Newborn altricial mammals need just after birth to locate their mother's nipples for suckling. In this precocious behavior, including for the human baby, maternal odor via the olfactory process plays a major role. Maternal odor emitted by lactating females or by amniotic fluid (AF) attracts pups, but the chemical identity of this attractant has not yet been elucidated. Here, using behavioral tests and gas chromatography coupled with mass spectrometry (GC-MS) techniques, we show that AF extracts from rat pregnant female, nipples, ventral skin, milk, and nest extracts of mother contained 3-6 active substances. AF extracts contained 3 active compounds: ethylbenzene, benzaldehyde, and benzyl alcohol, and their mixture in similar proportions to those found in AF extracts, in a ratio, respectively, of 1:1:12 (700 ng), attracts pups as putative maternal attractant substances (MAS). These 3 AF substances have already been identified in milk, nipples, ventral wash, and nest extracts of mother, but not in feces. Moreover, anethole flavor incorporated in pregnant rat and mother's diet is also detected in AF, nipples, milk, and nest extracts and the pups are attracted to anethole odor, but not in the case of the no-anethole pups. MAS, combined with diet flavors present in the AF bath, represent olfactory signals as "maternal signature odors" (MSO) that are learned by fetus and pups. These findings open the way to improved understanding of the neurobiology of early olfactory learning and of the importance of evolutionarily conserved survival behavior in many mammal species.

SK channel blockade reverses cognitive and motor deficits induced by nigrostriatal dopamine lesions in rats.

Parkinson's disease has traditionally been viewed as a motor disorder caused by the loss of dopamine (DA) neurons. However, emotional and cognitive syndromes can precede the onset of the motor deficits and provide an opportunity for therapeutic intervention. Potassium channels have recently emerged as potential new targets in the treatment of Parkinson's disease. The selective blockade of small conductance calcium-activated K+ channels (SK channels) by apamin is known to increase burst firing in midbrain DA neurons and therefore DA release. We thus investigated the effects of systemic administration of apamin on the motor, cognitive deficits and anxiety present after bilateral nigrostriatal 6-hydroxydopamine (6-OHDA) lesions in rats. Apamin administration (0.1 or 0.3 mg/kg i.p.) counteracted the depression, anxiety-like behaviors evaluated on sucrose consumption and in the elevated plus maze, social recognition and spatial memory deficits produced by partial 6-OHDA lesions. Apamin also reduced asymmetric motor deficits on circling behavior and postural adjustments in the unilateral extensive 6-OHDA model. The partial 6-OHDA lesions (56% striatal DA depletion) produced 20% decrease of iodinated apamin binding sites in the substantia nigra pars compacta in correlation with the loss of tyrosine hydroxylase positive cells, without modifying apamin binding in brain regions receiving DAergic innervation. Striatal extracellular levels of DA, not detectable after 6-OHDA lesions, were enhanced by apamin treatment as measured by in vivo microdialysis. These results indicate that blocking SK channels may reinstate minimal DA activity in the striatum to alleviate the non-motor symptoms induced by partial striatal DA lesions.

Kv4 potassium channels modulate hippocampal EPSP-spike potentiation and spatial memory in rats.

Kv4 channels regulate the backpropagation of action potentials (b-AP) and have been implicated in the modulation of long-term potentiation (LTP). Here we showed that blockade of Kv4 channels by the scorpion toxin AmmTX3 impaired reference memory in a radial maze task. In vivo, AmmTX3 intracerebroventricular (i.c.v.) infusion increased and stabilized the EPSP-spike (E-S) component of LTP in the dentate gyrus (DG), with no effect on basal transmission or short-term plasticity. This increase in E-S potentiation duration could result from the combination of an increase in excitability of DG granular cells with a reduction of GABAergic inhibition, leading to a strong reduction of input specificity. Radioactive in situ hybridization (ISH) was used to evaluate the amounts of Kv4.2 and Kv4.3 mRNA in brain structures at different stages of a spatial learning task in naive, pseudoconditioned, and conditioned rats. Significant differences in Kv4.2 and Kv4.3 mRNA levels were observed between conditioned and pseudoconditioned rats. Kv4.2 and Kv4.3 mRNA levels were transiently up-regulated in the striatum, nucleus accumbens, retrosplenial, and cingulate cortices during early stages of learning, suggesting an involvement in the switch from egocentric to allocentric strategies. Spatial learning performance was positively correlated with the levels of Kv4.2 and Kv4.3 mRNAs in several of these brain structures. Altogether our findings suggest that Kv4 channels could increase the signal-to-noise ratio during information acquisition, thereby allowing a better encoding of the memory trace.

KCa2 channels transiently downregulated during spatial learning and memory in rats.

Small-conductance calcium-activated potassium channels (K(Ca)2) are essential components involved in the modulation of neuronal excitability, underlying learning and memory. Recent evidence suggests that K(Ca)2 channel activity reduces synaptic transmission in a postsynaptic NMDA receptor-dependent manner and is modulated by long-term potentiation. We used radioactive in situ hybridization and apamin binding to investigate the amount of K(Ca)2 subunit mRNA and K(Ca)2 proteins in brain structures involved in learning and memory at different stages of a radial-arm maze task in naive, pseudoconditioned, and conditioned rats. We observed significant differences in K(Ca)2.2 and K(Ca)2.3, but not K(Ca)2.1 mRNA levels, between conditioned and pseudoconditioned rats. K(Ca)2.2 levels were transiently reduced in the dorsal CA fields of the hippocampus, whereas K(Ca)2.3 mRNA levels were reduced in the dorsal and ventral CA fields of the hippocampus, entorhinal cortex, and basolateral amygdaloid nucleus in conditioned rats, during early stages of learning. Levels of apamin-binding sites displayed a similar pattern to K(Ca)2 mRNA levels during learning. Spatial learning performance was positively correlated with levels of apamin-binding sites and K(Ca)2.3 mRNA in the dorsal CA1 field and negatively correlated in the dorsal CA3 field. These findings suggest that K(Ca)2 channels are transiently downregulated in the early stages of learning and that regulation of K(Ca)2 channel levels is involved in the modification of neuronal substrates underlying new information acquisition.

Small-conductance Ca(2+)-activated K(+) channels: Heterogeneous affinity in rat brain structures and cognitive modulation by specific blockers.

Small-conductance calcium-activated potassium channels (K(Ca)2) generating the medium afterhyperpolarization seen after an action potential modulate the neuronal integration signal. The effects of two K(Ca)2 channel blockers, apamin, specific to K(Ca)2.2 and K(Ca)2.3 channels, and lei-Dab7, which binds to K(Ca)2.2 channels only, were compared to evaluate the involvement of K(Ca)2 channel subunits in behavior, spatial learning and memory in rats. Intracerebroventricular (9-5 ng) injections of lei-dab7 decreased locomotor activity, food intake and body weight in rats deprived of food. A dose of 3 ng lei-Dab7 had no effect on these types of behavior. We therefore used this dose for attention and memory tasks. No modification to attention or memory was observed in a spatial radial-arm maze task with rats given 3 ng lei-Dab7, whereas apamin (0.3 ng) improved reference memory and accelerated changes of strategy from egocentric to allocentric. These findings suggest that K(Ca)2.3 blockade improves memory in rats. Lei-Dab7 entirely outcompeted the binding of iodinated apamin to 64 brain structures (mean IC(50): 34.5 nM), although IC(50) values were highly variable. By contrast, overall IC(50) values for apamin were close to mean values (11.3 pM). The very low affinity of the hippocampus and neocortex for lei-Dab7 may account for the absence of a behavioral effect of this compound. The variability of IC(50) values suggests that K(Ca)2 channel composition varies considerably as a function of the brain structure considered.

Sensory asymmetries in the olfactory system underlie sexual pheromone communication in the cockroach Nauphoeta cinerea.

In most insect species, males process female sex pheromone information in specific macroglomeruli in the olfactory lobes of their brains. The purpose of this report is to present a novel system of pheromone perception. In Nauphoeta cinerea cockroaches, males produce sex pheromones that induce mating behavior in females but neither sex has macroglomeruli. In this study, we show that female N. cinerea show asymmetry in the number of glomeruli whereas males do not. Females have more glomeruli on the right side and amputation of the right antenna reduced female ability to find a male and mate whereas amputation of the left antenna did not. We show that a key factor in female mating behavior is perception of the male sex pheromone seducin by the right antenna and the asymmetrically organized deutocerebral glomeruli associated with it. In the symmetrical olfactory system of males the detection of seducin may be involved in establishing dominance hierarchies.

Morphology of the sternal and tergal glands producing the sexual pheromones and the aphrodisiacs among the cockroaches of the subfamily oxyhaloinae.

Among cockroaches in the subfamily of Oxyhaloinae, the adult males produce two essential and successively active chemical signals: the sex pheromone attracting females from a distance secreted by the sternal glands, and the aphrodisiac required for mating which is secreted by the tergal glands. The adult males of the seven species studied, Nauphoeta cinerea, Henschoutedenia flexivitta, Leucophaea maderae, Jagrehnia madecassa, Gromphadorhina portentosa, G. laevigata, and G. chopardi, possess well-developed sternal and tergal glands whose number varies according to the species and methods of mating (three to six sternal glands and four to seven tergal glands). These glands are basically composed of type three glandular units (glandular cell + duct cell) and type 2 cells (modified oenocytes) which exhibit no significant external cuticular modification except for tergite 2 of L. maderae. The extreme variance in development of these glands can be linked to sexual behavior. The hypothesis put forward here is that of a regressive evolution of the tergal glands, related to a modification of the role played by the aphrodisiacs which they secrete.

Cuticular hydrocarbon profiles of dominant versus subordinate male Nauphoeta cinerea cockroaches.

Interactions between male Nauphoeta cinerea cockroaches are characterized by an elaborate ritual that leads to a stable dominant-subordinate hierarchy between two individuals. Chemical signals involving volatile sex pheromones and cuticular hydrocarbons play an important role in establishing and maintaining dominance status. The present study was performed to identify cuticular hydrocarbons in two- and three-times dominant or subordinate individuals obtained by forcing dyadic encounters. Two methods, i.e., solid-phase microextraction (SPME) and organic solvent extraction, were used to isolate cuticular hydrocarbons. A total of 23 peaks of cuticular hydrocarbons were identified. Analysis showed quantitative differences in hydrocarbon profiles of three-times dominant and subordinate individuals according to extraction method and dominance status. Dominant individuals were characterized by higher proportions of the monomethylalkanes 11- and 13-MeC36, 13- and 15-MeC38, and 11-, 13-, and 15-MeC35, while subordinate individuals had higher proportions of the following monomethylalkanes: 7-, 9-. and 11-MeC31, 5-MeC31, 3- and 8-MeC32, and 9-, 10-, 11-, and 12-MeC32. Discussion focuses on the reliability of hydrocarbons as indicators of dominance status and on their correlation with physiological processes.