Characterization of the interactions between two sites of plasticity engaged during eyelid conditioning

Here, we investigate the involvement of two sites of plasticity in the learning and expression of a simple associative motor behavior—the classically conditioned eyelid response. While previous studies clearly demonstrate that lesions of the anterior interpositus nucleus of the cerebellum abolish learned responses and prevent subsequent learning, studies investigating the effects of lesions of the cerebellar cortex on learning and retention have produced discrepant results. We complement ablative lesion studies of the cortex with the use of reversible, pharmacological blockade of cerebellar cortical transmission to investigate the role of the cerebellar cortex in eyelid conditioning. We demonstrate that both pharmacological blockade as well as focused ablative lesions of the cortex abolish timed responses and unmask responses with a fixed, short latency that are not displayed by the intact animal. Pharmacological blockade of cerebellar cortex output at various stages of acquisition and extinction reveals appropriate, learning dependent changes in the amplitude and probability of short latency responses during training. Acquisition of both short latency as well as timed responses is prevented by ablative lesions of the anterior lobe of the cerebellar cortex. These convergent results from technically distinct methods of removing the influence of the cerebellar cortex from conditioned behavior are consistent with the proposal that (1) eyelid conditioning engages two cerebellar sites of plasticity-one in the cortex and one in the anterior interpositus nucleus, (2) plasticity in the cerebellar cortex is necessary for proper response timing, (3) plasticity in the nucleus mediates the short latency responses unmasked by lesions of the cerebellar cortex, and (4) cerebellar cortical output is necessary for the induction of plasticity in the nucleus. ^

Immediate and simultaneous sensory reorganization at cortical and subcortical levels of the somatosensory system

The occurrence of cortical plasticity during adulthood has been demonstrated using many experimental paradigms. Whether this phenomenon is generated exclusively by changes in intrinsic cortical circuitry, or whether it involves concomitant cortical and subcortical reorganization, remains controversial. Here, we addressed this issue by simultaneously recording the extracellular activity of up to 135 neurons in the primary somatosensory cortex, ventral posterior medial nucleus of the thalamus, and trigeminal brainstem complex of adult rats, before and after a reversible sensory deactivation was produced by subcutaneous injections of lidocaine. Following the onset of the deactivation, immediate and simultaneous sensory reorganization was observed at all levels of the somatosensory system. No statistical difference was observed when the overall spatial extent of the cortical (9.1 ± 1.2 whiskers, mean ± SE) and the thalamic (6.1 ± 1.6 whiskers) reorganization was compared. Likewise, no significant difference was found in the percentage of cortical (71.1 ± 5.2%) and thalamic (66.4 ± 10.7%) neurons exhibiting unmasked sensory responses. Although unmasked cortical responses occurred at significantly higher latencies (19.6 ± 0.3 ms, mean ± SE) than thalamic responses (13.1 ± 0.6 ms), variations in neuronal latency induced by the sensory deafferentation occurred as often in the thalamus as in the cortex. These data clearly demonstrate that peripheral sensory deafferentation triggers a system-wide reorganization, and strongly suggest that the spatiotemporal attributes of cortical plasticity are paralleled by subcortical reorganization.

Representation of sound localization cues in the auditory thalamus of the barn owl

Barn owls can localize a sound source using either the map of auditory space contained in the optic tectum or the auditory forebrain. The auditory thalamus, nucleus ovoidalis (N.Ov), is situated between these two auditory areas, and its inactivation precludes the use of the auditory forebrain for sound localization. We examined the sources of inputs to the N.Ov as well as their patterns of termination within the nucleus. We also examined the response of single neurons within the N.Ov to tonal stimuli and sound localization cues. Afferents to the N.Ov originated with a diffuse population of neurons located bilaterally within the lateral shell, core, and medial shell subdivisions of the central nucleus of the inferior colliculus. Additional afferent input originated from the ipsilateral ventral nucleus of the lateral lemniscus. No afferent input was provided to the N.Ov from the external nucleus of the inferior colliculus or the optic tectum. The N.Ov was tonotopically organized with high frequencies represented dorsally and low frequencies ventrally. Although neurons in the N.Ov responded to localization cues, there was no apparent topographic mapping of these cues within the nucleus, in contrast to the tectal pathway. However, nearly all possible types of binaural response to sound localization cues were represented. These findings suggest that in the thalamo-telencephalic auditory pathway, sound localization is subserved by a nontopographic representation of auditory space.

Structure and evolution of the compact radio source in NGC 1275.

Investigations of the fine-scale structure in the compact nucleus of the radio source 3C 84 in NGC 1275 (New General Catalogue number) are reported. Structural monitoring observations beginning as early as 1976, and continuing to the present, revealed subluminal motions in a jet-like relatively diffuse region extending away from a flat-spectrum core. A counterjet feature was discovered in 1993, and very recent nearly simultaneous studies have detected the same feature at five frequencies ranging from 5 to 43 GHz. The counterjet exhibits a strong low-frequency cutoff, giving this region of the source an inverted spectrum. The observations are consistent with a physical model in which the cutoff arises from free-free absorption in a volume that surrounds the core but obscures only the counterjet feature. If such a model is confirmed, very-long-baseline radio interferometry observations can then be used to probe the accretion region, outside the radio jet, on parsec scales.

Medial prefrontal cortex suppression of the hypothalamic–pituitary–adrenal axis response to a physical stressor, systemic delivery of interleukin-1β

Previous studies have shown that the medial prefrontal cortex can suppress the hypothalamic-pituitary-adrenal axis response to stress. However, this effect appears to vary with the type of stressor. Furthermore, the absence of direct projections between the medial prefrontal cortex and corticotropin-releasing factor cells at the apex of the hypothalamic-pituitary-adrenal axis suggest that other brain regions must act as a relay when this inhibitory mechanism is activated. In the present study, we first established that electrolytic lesions involving the prelimbic and infralimbic medial prefrontal cortex increased plasma adrenocorticotropic hormone levels seen in response to a physical stressor, the systemic delivery of interleukin-1beta. However, medial prefrontal cortex lesions did not alter plasma adrenocorticotropic hormone levels seen in response to a psychological stressor, noise. To identify brain regions that might mediate the effect of medial prefrontal cortex lesions on hypothalamic-pituitary-adrenal axis responses to systemic interleukin-1beta, we next mapped the effects of similar lesions on interleukin-1beta-induced Fos expression in regions previously shown to regulate the hypothalamic-pituitary-adrenal axis response to this stressor. It was found that medial prefrontal cortex lesions reduced the number of Fos-positive cells in the ventral aspect of the bed nucleus of the stria terminalis. However, the final experiment, which involved combining retrograde tracing with Fos immunolabelling, revealed that bed nucleus of the stria terminalis-projecting medial prefrontal cortex neurons were largely separate from medial prefrontal cortex neurons recruited by systemic interleukin-1beta, an outcome that is difficult to reconcile with a simple medial prefrontal cortex-bed nucleus of the stria terminalis-corticotropin-releasing factor cell control circuit.

Spiking neuron models of the medial and lateral superior olive for sound localisation

Sound localisation is defined as the ability to identify the position of a sound source. The brain employs two cues to achieve this functionality for the horizontal plane, interaural time difference (ITD) by means of neurons in the medial superior olive (MSO) and interaural intensity difference (IID) by neurons of the lateral superior olive (LSO), both located in the superior olivary complex of the auditory pathway. This paper presents spiking neuron architectures of the MSO and LSO. An implementation of the Jeffress model using spiking neurons is presented as a representation of the MSO, while a spiking neuron architecture showing how neurons of the medial nucleus of the trapezoid body interact with LSO neurons to determine the azimuthal angle is discussed. Experimental results to support this work are presented.

Absence of LPA1 receptor results in altered pattern of limbic activation after tail suspension test

Stress serves as an adaptive mechanism and helps organisms to cope with life-threatening situations. However, individual vulnerability to stress and dysregulation of this system may precipitate stress-related disorders such as depression. The neurobiological circuitry in charge of dealing with stressors has been widely studied in animal models. Recently our group has demonstrated a role for lysophosphatidic acid (LPA) through the LPA1 receptor in vulnerability to stress, in particular the lack of this receptor relates to robust decrease of adult hippocampal neurogenesis and induction of anxious and depressive states. Nevertheless, the specific abnormalities in the limbic circuit in reaction to stress remains unclear. The aim of this study is to examine the differences in the brain activation pattern in the presence or absence of LPA1 receptor after acute stress. For this purpose, we have studied the response of maLPA1-null male mice and normal wild type mice to an intense stressor: Tail Suspension Test. Activation induced by behaviour of brain regions involved in mood regulation was analysed by stereological quantification of c-Fos immunoreactive positive cells. We also conducted multidimensional scaling analysis in order to unravel coativation between structures. Our results revealed hyperactivity of stress-related structures such as amygdala and paraventricular nucleus of the hypothalamus in the knockout model and different patterns of coactivation in both genotypes using a multidimensional map. This data provides further evidence to the engagement of the LPA1 receptors in stress regulation and sheds light on different neural pathways under normal and vulnerability conditions that can lead to mood disorders.

Corticotrophin-releasing factor mediates hypophagia after adrenalectomy, increasing meal-related satiety responses

Adrenalectomy-induced hypophagia is associated with increased satiety-related responses, which involve neuronal activation of the nucleus of the solitary tract (NTS). Besides its effects on the pituitary-adrenal axis, corticotrophin-releasing factor (CRF) has been shown to play an important role in feeding behaviour, as it possesses anorexigenic effects. We evaluated feeding-induced CRF mRNA expression in the paraventricular nucleus (PVN) and the effects of pretreatment with CRF(2) receptor antagonist (Antisauvagine-30, AS30) on food intake and activation of NTS neurons in response to feeding in adrenalectomised (ADX) rats. Compared to the sham group, ADX increased CRF mRNA levels in the PVN of fasted animals, which was further augmented by refeeding. AS30 treatment did not affect food intake in the sham and ADX + corticosterone (B) groups; however, it reversed hypophagia in the ADX group. In vehicle-pretreated animals, refeeding increased the number of Fos and Fos/TH-immunoreactive neurons in the NTS in the sham, ADX and ADX + B groups, with the highest number of neurons in the ADX animals. Similarly to its effect on food intake, pretreatment with AS30 in the ADX group also reversed the increased activation of NTS neurons induced by refeeding while having no effect in the sham and ADX + B animals. The present results show that adrenalectomy induces an increase in CRF mRNA expression in the PVN potentiated by feeding and that CRF(2) receptor antagonist abolishes the anorexigenic effect and the increased activation of NTS induced by feeding in the ADX animals. These data indicate that increased activity of PVN CRF neurons modulates brainstem satiety-related responses, contributing to hypophagia after adrenalectomy. (C) 2010 Elsevier Inc. All rights reserved.

A Zona Incerta no sagüi (Callithrix jacchus): Análise Citoarquitetônica, Neuroquímica e Projeção Retiniana

The retinal projections in mammals usually reach, classically, three major functional systems: the primary visual system, the accessory optic system, and the circadian timing system. But the retinal projections also reach areas classically considered non-visual, one of which groups the neurons of the zona incerta (ZI), target this study. The primary visual system includes thalamic lateral geniculate complex is formed by the dorsal lateral geniculate nucleus, intergeniculate leaflet and the ventral lateral geniculate nucleus and other Components. The accessory optic system is composed of the small nuclei: nuclei terminal dorsal, lateral, medial and the interstitial nucleus of the superior posterior fasciculus. These nuclei are involved in visuo-motor activities. The circadian timing system is comprised of the suprachiasmatic nucleus of the hypothalamus, that act as master circadian pacemaker, entraining pathways and efferents pathways to the efectors, and the intergeniculate leaflet, that seems to act as a modulator of the pacemaker. The retinal projections too reach classically considered non-visual areas, including the zona incerta. This region is localized in the ventral thalamus and has been implicated in various functional properties including nociceptive and somatosensory processing, motor response, sociosexual behaviour, feeding and drinking, in symptoms of neurodegenerative diseases, arousal and attention. It also displays connection with several areas of central nervous system. The aim of this study was characterize the retinal projection in the zona incerta of Callithrix jacchus (sagüi), a primate of the New World through the anterograde axonal transport of the cholera toxin subunit b and analyze the citoarchicteture using Nissl and NeuN, and neurochemical substances such as serotonin, GABA, VIP, VP, GFAP and binding-calcium proteins. The zona incerta showed a different division of the literature in citoarquitetura, both by means of Nissl as neurochemical by NeuN, with a subdivision ventrolateral and dorsomedial. The neurochemical to the other substances corroborate with this subdivision. The GFAP was almost completely negative for the zona incerta, result non evidenced in previous studies yet. The 16 retinal projection in sagüi, unlike other primates and rodents, reached the caudal portion only. This work helps to make further studies are conducted based on this subdivision and the localization of the neurochemical substances associated with possible behaviors that the zona incerta is involved

Oxytocinergic and serotonergic systems involvement in sodium intake regulation: satiety or hypertonicity markers?

Previous studies demonstrated the inhibitory participation of serotonergic ( 5-HT) and oxytocinergic (OT) neurons on sodium appetite induced by peritoneal dialysis (PD) in rats. The activity of 5-HT neurons increases after PD- induced 2% NaCl intake and decreases after sodium depletion; however, the activity of the OT neurons appears only after PD-induced 2% NaCl intake. To discriminate whether the differential activations of the 5-HT and OT neurons in this model are a consequence of the sodium satiation process or are the result of stimulation caused by the entry to the body of a hypertonic sodium solution during sodium access, we analyzed the number of Fos-5-HT- and Fos-OT-immunoreactive neurons in the dorsal raphe nucleus and the paraventricular nucleus of the hypothalamus-supraoptic nucleus, respectively, after isotonic vs. hypertonic NaCl intake induced by PD. We also studied the OT plasma levels after PD- induced isotonic or hypertonic NaCl intake. Sodium intake induced by PD significantly increased the number of Fos-5- HT cells, independently of the concentration of NaCl consumed. In contrast, the number of Fos-OT neurons increased after hypertonic NaCl intake, in both depleted and nondepleted animals. The OT plasma levels significantly increased only in the PD- induced 2% NaCl intake group in relation to others, showing a synergic effect of both factors. In summary, 5-HT neurons were activated after body sodium status was reestablished, suggesting that this system is activated under conditions of satiety. In terms of the OT system, both OT neural activity and OT plasma levels were increased by the entry of hypertonic NaCl solution during sodium consumption, suggesting that this system is involved in the processing of hyperosmotic signals.

Galanin regulates prolactin release and lactotroph proliferation

The neuropeptide galanin is predominantly expressed by the lactotrophs (the prolactin secreting cell type) in the rodent anterior pituitary and in the median eminence and paraventricular nucleus of the hypothalamus. Prolactin and galanin colocalize in the same secretory granule, the expression of both proteins is extremely sensitive to the estrogen status of the animal. The administration of estradiol-17β induces pituitary hyperplasia followed by adenoma formation and causes a 3,000-fold increase in the galanin mRNA content of the lactotroph. To further study the role of galanin in prolactin release and lactotroph growth we now report the generation of mice carrying a loss-of-function mutation of the endogenous galanin gene. There is no evidence of embryonic lethality and the mutant mice grow normally. The specific endocrine abnormalities identified to date, relate to the expression of prolactin. Pituitary prolactin message levels and protein content of adult female mutant mice are reduced by 30–40% compared with wild-type controls. Mutant females fail to lactate and pups die of starvation/dehydration unless fostered onto wild-type mothers. Prolactin secretion in mutant females is markedly reduced at 7 days postpartum compared with wild-type controls with an associated failure in mammary gland maturation. There is an almost complete abrogation of the proliferative response of the lactotroph to high doses of estrogen, with a failure to up-regulate prolactin release, STAT5 expression or to increase pituitary cell number. These data further support the hypothesis that galanin acts as a paracrine regulator of prolactin expression and as a growth factor to the lactotroph.

Refractoriness to melatonin occurs independently at multiple brain sites in Siberian hamsters

The mid-winter development of refractoriness to melatonin (Mel) triggers recrudescence of the atrophied reproductive apparatus of rodents. As a consequence, over-wintering animals become reproductively competent just before the onset of spring conditions favorable for breeding. The neural target tissues that cease to respond to winter Mel signals have not been identified. We now report that the suprachiasmatic nucleus of the hypothalamus, which contains the principal circadian clock, and the reuniens and paraventricular nuclei of the thalamus, each independently becomes refractory to melatonin. Small implants of Mel that were left in place for 40 wk and that act locally on these brain nuclei, induced testicular regression within 6 wk in male Siberian hamsters; 12 wk later Mel implants no longer suppressed reproduction and gonadal recrudescence ensued. Hamsters that were then given a systemic Mel infusion s.c. immediately initiated a second gonadal regression, implying that neurons at each site become refractory to Mel without compromising responsiveness of other Mel target tissues. Refractoriness occurs locally and independently at each neural target tissue, rather than in a separate “refractoriness” substrate. Restricted, target-specific actions of Mel are consistent with the independent regulation by day length of the several behavioral and physiological traits that vary seasonally in mammals.

Influência dos odores de gato e de cobra no comportamento defensivo e expressão de fos do sistema hipotalâmico de defesa de camundongo

Studies using neuronal tract-tracer in rat have shown that the anterior hypothalamic nucleus, dorsomedial division of the ventromedial nucleus of the hypothalamus and dorsal premammillary nucleus are highly connected. When the rat is exposed to predator or its odor these nuclei have shown a expression of Fos and their lesion reduces defensive behavior against predator. This set of nuclei was named the Hypothalamic Defense System. However, little is known about the response of this system to the odor of different predators or its role in mice. In this work, we exposed Swiss mice to two different predators odor (cat and snake) to verify the Fos expression in the Hypothalamic Defense System, as well as the defensive behaviors displayed. The analysis showed that the mice exposure to cat odor had an increased expression of Fos protein compared to control, while those exposed to snake odor showed no rise in Fos expression, which was corroborated by the behavioral data. Our results indicate that this distinct circuit in mice seems to act differentially to odorous stimuli of different predators, causing distinct behavioral responses of mice and that the odor of snake seems not to be perceived by Swiss mice as a threatening stimulus.

Dipeptidyl peptidase IV in the hypothalamus and hippocampus of monosodium glutamate obese and food-deprived rats

Proline-specific dipeptidyl peptidases are emerging as a protease family with important roles in the regulation of signaling by peptide hormones related to energy balance. The treatment of neonatal rats with monosodium glutamate (MSG) is known to produce a selective damage on the arcuate nucleus with development of obesity. This study investigates the relationship among dipeptidyl peptidase IV (DPPIV) hydrolyzing activity, CD26 protein, fasting, and MSG model of obesity in 2 areas of the central nervous system. Dipeptidyl peptidase IV and CD26 were, respectively, evaluated by fluorometry, and enzyme-linked immunosorbent assay and reverse transcriptase polymerase chain reaction in soluble (SF) and membrane-bound (MF) fractions from the hypothalamus and hippocampus of MSG-treated and normal rats, submitted or not to food deprivation (FD). Dipeptidyl peptidase IV in both areas was distinguished kinetically as insensitive (DI) and sensitive (DS) to diprotin A. Compared with the controls, MSG and/or FD decreased the activity of DPPIV-DI in the SF and MF from the hypothalamus, as well as the activity of DPPIV-DS in the SF from the hypothalamus and in the MF from the hippocampus. Monosodium glutamate and/or FD increased the activity of DPPIV-DI in the MF from the hippocampus. The monoclonal protein expression of membrane CD26 by enzyme-linked immunosorbent assay decreased in the hypothalamus and increased in the hippocampus of MSG and/or FD relative to the controls. The existence of DPPIV-like activity with different sensitivities to diprotin A and the identity of insensitive with CD26 were demonstrated for the first time in the central nervous system. Data also demonstrated the involvement of DPPIV-DI/CD26 hydrolyzing activity in the energy balance probably through the regulation of neuropeptide Y and beta-endorphin levels in the hypothalamus and hippocampus. (C) 2011 Elsevier Inc. All rights reserved.

APM/CD13 and FOS in the hypothalamus of monosodium glutamate obese and food deprived rats

Protein (western blotting) and gene (PCR) expressions, catalytic activity of puromycin-insensitive membrane-bound neutral aminopeptidase (APM/CD13) and in situ regional distribution of CD13 and FOS immunoreactivity (it) were evaluated in the hypothalamus of monosodium glutamate obese (MSG) and/or food deprived (FD) rats in order to investigate their possible interplay with metabolic functions. Variations in protein and gene expressions of CD13 relative to controls coincided in the hypothalamus of MSG and MSG-FD (decreased 2- to 17-fold). Compared with controls, the reduction of hypothalamic CD13 content reflected a negative balance in its regional distribution in the supraoptic, paraventricular, periventricular and arcuate nuclei. CD13-ir increased in the supraoptic nucleus in MSG (2.5-fold) and decreased in the paraventricular nucleus (2-fold) together with FOS-ir (1.5-fold) in FD. In MSG-FD. FOS-ir decreased (7-fold) in the paraventricular nucleus, while CD13-ir decreased in the periventricular (5.6-fold) and the arcuate (3.7-fold) nuclei. It was noteworthy that all these changes of CD13 were not related to catalytic activity of APM. Data suggested that hypothalamic CD13 plays a role in the regulation of energy metabolism not by means of APM enzyme activity. (c) 2010 Elsevier B.V. All rights reserved.