Brain activity underlying American crow processing of encounters with dead conspecifics.

Animals utilize a variety of auditory and visual cues to navigate the landscape of fear. For some species, including corvids, dead conspecifics appear to act as one such visual cue of danger, and prompt alarm calling by attending conspecifics. Which brain regions mediate responses to dead conspecifics, and how this compares to other threats, has so far only been speculative. Using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) we contrast the metabolic response to visual and auditory cues associated with a dead conspecific among five a priori selected regions in the American crow (Corvus brachyrhynchos) brain: the hippocampus, nidopallium caudolaterale, striatum, amygdala, and the septum. Using a repeated-measures, fully balanced approach, we exposed crows to four stimuli: a dead conspecific, a dead song sparrow (Melospiza melodia), conspecific alarm calls given in response to a dead crow, and conspecific food begging calls. We find that in response to observations of a dead crow, crows show significant activity in areas associated with higher-order decision-making (NCL), but not in areas associated with social behaviors or fear learning. We do not find strong differences in activation between hearing alarm calls and food begging calls; both activate the NCL. Lastly, repeated exposures to negative stimuli had a marginal effect on later increasing the subjects' brain activity in response to control stimuli, suggesting that crows might quickly learn from negative experiences.

Electroacupuncture in rats normalizes the diabetes-induced alterations in the septo-hippocampal cholinergic system.

Diabetes induces early sufferance in the cholinergic septo-hippocampal system, characterized by deficits in learning and memory, reduced hippocampal plasticity and abnormal pro-nerve growth factor (proNGF) release from hippocampal cells, all linked to dysfunctions in the muscarinic cholinergic modulation of hippocampal physiology. These alterations are associated with dysregulation of several cholinergic markers, such as the NGF receptor system and the acetylcholine biosynthetic enzyme choline-acetyl transferase (ChAT), in the medial septum and its target, the hippocampus. Controlled and repeated sensory stimulation by electroacupuncture has been proven effective in counteracting the consequences of diabetes on cholinergic system physiology in the brain. Here, we used a well-established Type 1 diabetes model, obtained by injecting young adult male rats with streptozotocin, to induce sufferance in the septo-hippocampal system. We then evaluated the effects of a 3-week treatment with low-frequency electroacupuncture on: (a) the expression and protein distribution of proNGF in the hippocampus, (b) the tissue distribution and content of NGF receptors in the medial septum, (c) the neuronal cholinergic and glial phenotype in the septo-hippocampal circuitry. Twice-a-week treatment with low-frequency electroacupuncture normalized, in both hippocampus and medial septum, the ratio between the neurotrophic NGF and its neurotoxic counterpart, the precursor proNGF. Electroacupuncture regulated the balance between the two major proNGF variants (proNGF-A and proNGF-B) at both gene expression and protein synthesis levels. In addition, electroacupuncture recovered to basal level the pro-neurotrophic NGF receptor tropomyosin receptor kinase-A content, down-regulated in medial septum cholinergic neurons by diabetes. Electroacupuncture also regulated ChAT content in medial septum neurons and its anterograde transport toward the hippocampus. Our data indicate that repeated sensory stimulation can positively affect brain circuits involved in learning and memory, reverting early impairment induced by diabetes development. Electroacupuncture could exert its effects on the septo-hippocampal cholinergic neurotransmission in diabetic rats, not only by rescuing the hippocampal muscarinic responsivity, as previously described, but also normalizing acetylcholine biosynthesis and NGF metabolism in the hippocampus.

Mapping the brain of the chicken (Gallus gallus), with emphasis on the septal-hypothalamic region.

There has been remarkable progress in discoveries made in the avian brain, particularly over the past two decades. This review first highlights some of the discoveries made in the forebrain and credits the Avian Brain Nomenclature Forum, responsible for changing many of the terms found in the cerebrum and for stimulating collaborative research thereafter. The Forum facilitated communication among comparative neurobiologists by eliminating confusing and inaccurate names. The result over the past 15yearshas been a standardized use of avian forebrain terms. Nonetheless, additional changes are needed. The goal of the paper is to encourage a continuing effort to unify the nomenclature throughout the entire avian brain. To emphasize the need for consensus for a single name for each neural structure, I have selected specific structures in the septum and hypothalamus that our laboratory has been investigating, to demonstrate a lack of uniformity in names applied to conservative brain regions compared to the forebrain. The specific areas reviewed include the distributions of gonadotropin-releasing hormone neurons and their terminal fields in circumventricular organs, deep-brain photoreceptors, gonadotropin inhibitory neurons and a complex structure and function of the nucleus of the hippocampal commissure.

Widespread blunting of hypothalamic and amygdala-septal activity and behavior in rats with long-term hyperglycemia.

Anxiety and depression in diabetic patients contributes to a poor prognosis, but possible causal relationships have been controversial. Anxiety, fear, and anhedonia are mediated by interactions between different deep structures of the temporal lobe (e.g., amygdala complex and hippocampus) and other forebrain-related structures (e.g., lateral septal nucleus). Connections between these structures and the hypothalamic orexinergic system are necessary for the maintenance of energy and wakefulness. However, few studies have explored the impact of long-term hyperglycemia in these structures on anxiety. We induced long-term hyperglycemia (glucose levels of ∼500mg/dl) in Wistar rats by injecting them with alloxan and simultaneously protecting them from hyperglycemia by injecting them daily with a low dose of insulin (i.e., just enough insulin to avoid death), thus maintaining hyperglycemia and ketonuria for as long as 6 weeks. Compared with controls, long-term hyperglycemic rats exhibited a significant reduction of Fos expression in the lateral septal nucleus and basolateral amygdala, but no differences were found in cerebellar regions. Orexin-A cells appeared to be inactive in the lateral hypothalamus. No differences were found in sucrose consumption or behavior in the elevated plus maze compared with the control group, but a decrease in general locomotion was observed. These data indicate a generalized blunting of the metabolic brain response, accompanied by a decrease in locomotion but no changes in hedonic- or anxiety-like behavior.

Tracking the fear memory engram: discrete populations of neurons within amygdala, hypothalamus, and lateral septum are specifically activated by auditory fear conditioning.

Memory formation is thought to occur via enhanced synaptic connectivity between populations of neurons in the brain. However, it has been difficult to localize and identify the neurons that are directly involved in the formation of any specific memory. We have previously used fos-tau-lacZ (FTL) transgenic mice to identify discrete populations of neurons in amygdala and hypothalamus, which were specifically activated by fear conditioning to a context. Here we have examined neuronal activation due to fear conditioning to a more specific auditory cue. Discrete populations of learning-specific neurons were identified in only a small number of locations in the brain, including those previously found to be activated in amygdala and hypothalamus by context fear conditioning. These populations, each containing only a relatively small number of neurons, may be directly involved in fear learning and memory.

Morphine causes persistent induction of nitrated neurofilaments in cortex and subcortex even during abstinence.

Morphine has a profound role in neurofilament (NF) expression. However, there are very few studies on the fate of NFs during morphine abstinence coinciding with periods of relapse. Mice were treated chronically with morphine to render them tolerant to and dependent on morphine and sacrificed thereafter while another group, treated similarly, was left for 2 months without morphine. A long-lasting alteration in the stoichiometric ratio of the three NFs was observed under both conditions in both the cortex and subcortex. Morphine abstinence caused significant alterations in the phosphorylated and nitrated forms of the three NF subunits. Nitrated neurofilament light polypeptide chain (NFL) was significantly increased during chronic morphine treatment which persisted even after 2 months of morphine withdrawal. Mass spectrometric analysis following two-dimensional gel electrophoresis (2DE)-gel electrophoresis of cytoskeleton fractions of both cortex and subcortex regions identified enzymes associated with energy metabolism, cytoskeleton-associated proteins as well as NFs which showed sustained regulation even after abstinence of morphine for 2 months. It is suggestive that alteration in the levels of some of these proteins may be instrumental in the increased nitration of NFL during morphine exposure. Such gross alteration in NF dynamics is indicative of a concerted biological process of neuroadaptation during morphine abstinence.

The impact of television viewing on brain structures: cross-sectional and longitudinal analyses.

Television (TV) viewing is known to affect children's verbal abilities and other physical, cognitive, and emotional development in psychological studies. However, the brain structural development associated with TV viewing has never been investigated. Here we examined cross-sectional correlations between the duration of TV viewing and regional gray/white matter volume (rGMV/rWMV) among 133 boys and 143 girls as well as correlations between the duration of TV viewing and longitudinal changes that occurred a few years later among 111 boys and 105 girls. After correcting for confounding factors, we found positive effects of TV viewing on rGMV of the frontopolar and medial prefrontal areas in cross-sectional and longitudinal analyses, positive effects of TV viewing on rGMV/rWMV of areas of the visual cortex in cross-sectional analyses, and positive effects of TV viewing on rGMV of the hypothalamus/septum and sensorimotor areas in longitudinal analyses. We also confirmed negative effects of TV viewing on verbal intelligence quotient (IQ) in cross-sectional and longitudinal analyses. These anatomical correlates may be linked to previously known effects of TV viewing on verbal competence, aggression, and physical activity. In particular, the present results showed effects of TV viewing on the frontopolar area of the brain, which has been associated with intellectual abilities.

Control of stress-induced persistent anxiety by an extra-amygdala septohypothalamic circuit.

The extended amygdala has dominated research on the neural circuitry of fear and anxiety, but the septohippocampal axis also plays an important role. The lateral septum (LS) is thought to suppress fear and anxiety through its outputs to the hypothalamus. However, this structure has not yet been dissected using modern tools. The type 2 CRF receptor (Crfr2) marks a subset of LS neurons whose functional connectivity we have investigated using optogenetics. Crfr2(+) cells include GABAergic projection neurons that connect with the anterior hypothalamus. Surprisingly, we find that these LS outputs enhance stress-induced behavioral measures of anxiety. Furthermore, transient activation of Crfr2(+) neurons promotes, while inhibition suppresses, persistent anxious behaviors. LS Crfr2(+) outputs also positively regulate circulating corticosteroid levels. These data identify a subset of LS projection neurons that promote, rather than suppress, stress-induced behavioral and endocrinological dimensions of persistent anxiety states and provide a cellular point of entry to LS circuitry.

Regional and subtype-specific loss of GnRH neurons is associated with diminished mating behavior in middle-aged male rats.

The current study was to examine the relationship between the number of gonadotropin-releasing hormone (GnRH) neurons and male sexual behavior in middle-aged rats. Based on their sexual performance, middle-aged male rats (18-19 months) were assigned to three groups: (i) Group MIE (showing mounts, intromissions, and ejaculation), (ii) Group MI (displaying mounts and intromissions, but no ejaculation), and (iii) Group NC (showing no copulatory behavior). The brains of these middle-aged animals and of sexually active, young controls were collected and then examined for immunohistochemical localization of GnRH neurons. The numbers of two subtypes of GnRH neurons, smooth (s-GnRH) and irregular (i-GnRH), in the medial septum (MS), organum vasculosum of the lamina terminalis (OVLT), preoptic area (POA), and anterior hypothalamus (AH), were determined under a light microscope. As compared to young controls, an age-related decrease in the number of s-GnRH neurons was found in the MS of MIE rats. Among three groups of middle-aged rats, Groups MIE and MI had more s-GnRH neurons in the POA and i-GnRH neurons in the OVLT and POA than Group NC. In addition, loss of s-GnRH and i-GnRH neurons in the MS was observed in Groups MI and NC and Group NC, respectively. Our results suggest that a decrease in GnRH neuron subtypes occurring in different brain regions might be critical for the loss of specific components of male rat sexual behavior during aging.

On lateral septum-like characteristics of outputs from the accumbal hedonic "hotspot" of Peciña and Berridge with commentary on the transitional nature of basal forebrain "boundaries".

Peciña and Berridge (2005; J Neurosci 25:11777-11786) observed that an injection of the µ-opioid receptor agonist DAMGO (D-ala(2) -N-Me-Phe(4) -Glycol(5) -enkephalin) into the rostrodorsal part of the accumbens shell (rdAcbSh) enhances expression of hedonic "liking" responses to the taste of an appetitive sucrose solution. Insofar as the connections of this hedonic "hotspot" were not singled out for special attention in the earlier neuroanatomical literature, we undertook to examine them. We observed that the patterns of inputs and outputs of the rdAcbSh are not qualitatively different from those of the rest of the Acb, except that outputs from the rdAcbSh to the lateral preoptic area and anterior and lateral hypothalamic areas are anomalously robust and overlap extensively with those of the lateral septum. We also detected reciprocal interconnections between the rdAcbSh and lateral septum. Whether and how these connections subserve hedonic impact remains to be learned, but these observations lead us to hypothesize that the rdAcbSh represents a basal forebrain transition area, in the sense that it is invaded by neurons of the lateral septum, or possibly transitional neuronal forms sharing properties of both structures. We note that the proposed transition zone between lateral septum and rdAcbSh would be but one of many in the basal forebrain and conclude by reiterating the longstanding argument that the transitional nature of such boundary areas has functional importance, of which the precise nature will remain elusive until the neurophysiological and neuropharmacological implications of such zones of transition are more generally acknowledged and better addressed.

[Detection of c-fos expression in animal brain in a pilocarpine model of temporal lobe epilepsy].

The dynamics of the involvement of different brain structures in a pathological process is very important for decoding the mechanisms of temporal lobe epilepsy. In this work, the experimental model of temporal lobe epilepsy induced by lithium chloride and pilocarpine was used. The method of immunochemical detection of the immediate early gene c-fos was used as an indicator of functioning neurons in the brain. The c-fos expression was determined at different time points (30, 60 and 90 min) after the pilocarpine injection. An increase in the c-fos expression was observed in neuronal populations during the development of the status epilepticus, the time and degree of involvement of different brain structures being different. The expression of c-fos was first observed in the piriform cortex, the olfactory tubercle, thalamic nuclei, lateral habenular nuclei, and the caudate putamen. Then the hippocampus, the septal formation, the amygdala, and basal ganglia were involved in the activation process. In the hypothalamic areas, c-fos expression was observed latest. These data contribute to understanding the mechanisms of temporal lobe epilepsy and searching for the ways of its therapy.

Use of a micromanipulator system (NeuRobot) in endoscopic neurosurgery.

NeuRobot, a micromanipulator system with a rigid neuroendoscope and three micromanipulators, was developed for less invasive and telecontrolled neurosurgery. This system can be used to perform sophisticated surgical procedures through a small, 10-mm-diameter, window. The present study was performed to evaluate the feasibility of using NeuRobot in neuroendoscopy. Four different intraventricular neurosurgical procedures were simulated in three fixed cadaver heads using NeuRobot: (1) fenestration of the floor of the third ventricle; (2) fenestration of the septum pellucidum; (3) biopsy of the thalamus; and (4) biopsy of the choroid plexus of the lateral ventricle. Each procedure required less than 2 min, and all procedures were performed accurately. After these surgical simulations, a third ventriculostomy was carried out safely and adequately in a patient with obstructive hydrocephalus due to a midbrain venous angioma. Our results confirmed that NeuRobot is applicable to lesions in which conventional endoscopic neurosurgery is indicated. Furthermore, NeuRobot can perform more complex surgical procedures than a conventional neuroendoscope because of its maneuverability and stability. NeuRobot will become a useful neurosurgical tool for dealing with lesions that are difficult to treat by conventional neuroendoscopic surgery.

Guilt-selective functional disconnection of anterior temporal and subgenual cortices in major depressive disorder.

CONTEXT: Proneness to overgeneralization of self-blame is a core part of cognitive vulnerability to major depressive disorder (MDD) and remains dormant after remission of symptoms. Current neuroanatomical models of MDD, however, assume general increases of negative emotions and are unable to explain biases toward emotions entailing self-blame (eg, guilt) relative to those associated with blaming others (eg, indignation). Recent functional magnetic resonance imaging (fMRI) studies in healthy participants have shown that moral feelings such as guilt activate representations of social meaning within the right superior anterior temporal lobe (ATL). Furthermore, this area was selectively coupled with the subgenual cingulate cortex and adjacent septal region (SCSR) during the experience of guilt compared with indignation. Despite its psychopathological importance, the functional neuroanatomy of guilt in MDD is unknown. OBJECTIVE: To use fMRI to test the hypothesis that, in comparison with control individuals, participants with remitted MDD exhibit guilt-selective SCSR-ATL decoupling as a marker of deficient functional integration. DESIGN: Case-control study from May 1, 2008, to June 1, 2010. SETTING: Clinical research facility. PARTICIPANTS: Twenty-five patients with remitted MDD (no medication in 16 patients) with no current comorbid Axis I disorders and 22 controls with no personal or family history of MDD. MAIN OUTCOME MEASURES: Between-group difference of ATL coupling with a priori SCSR region of interest for guilt vs indignation. RESULTS: We corroborated the prediction of a guilt-selective reduction in ATL-SCSR coupling in MDD vs controls (familywise error-corrected P=.001 over the region of interest) and revealed additional medial frontopolar, right hippocampal, and lateral hypothalamic areas of decoupling while controlling for medication status and intensity of negative emotions. Lower levels of ATL-SCSR coupling were associated with higher scores on a validated measure of overgeneralized self-blame (67-item Interpersonal Guilt Questionnaire). CONCLUSIONS: Vulnerability to MDD is associated with temporofrontolimbic decoupling that is selective for self-blaming feelings. This provides the first neural mechanism ofMDD vulnerability that accounts for self-blaming biases.

A septal-hypothalamic pathway drives orexin neurons, which is necessary for conditioned cocaine preference.

Orexins (also called hypocretins) have been shown to be importantly involved in reward and addiction, but little is known about the circuitry that regulates orexin neuronal activity during drug-seeking behaviors. Here, we examined inputs to the lateral hypothalamus (LH) orexin cell field from the lateral septum (LS) using tract-tracing and Fos immunohistochemistry after cocaine (10 mg/kg) conditioned place preference (CPP) in Sprague Dawley rats. We found that neurons in rostral LS (LSr) that project to LH are Fos-activated in proportion to cocaine CPP, and that inhibition of LSr neurons with local baclofen and muscimol microinjection (0.3/0.03 nmol) blocks expression of Fos in LH orexin cells and cocaine preference. In addition, using local inactivation in LS and orexin antisense morpholinos in LH, we found that LSr influences on LH orexin neurons are critical for the expression of cocaine preference. These results indicate that LSr activates LH orexin neurons during cocaine place preference, and that this circuit is essential for expression of cocaine place preference.

Distribution of type 1 cannabinoid receptor-expressing neurons in the septal-hypothalamic region of the mouse: colocalization with GABAergic and glutamatergic markers.

Type 1 cannabinoid receptor (CB1) is the principal mediator of retrograde endocannabinoid signaling in the brain. In this study, we addressed the topographic distribution and amino acid neurotransmitter phenotype of endocannabinoid-sensitive hypothalamic neurons in mice. The in situ hybridization detection of CB1 mRNA revealed high levels of expression in the medial septum (MS) and the diagonal band of Broca (DBB), moderate levels in the preoptic area and the hypothalamic lateroanterior (LA), paraventricular (Pa), ventromedial (VMH), lateral mammillary (LM), and ventral premammillary (PMV) nuclei, and low levels in many other hypothalamic regions including the suprachiasmatic (SCh) and arcuate (Arc) nuclei. This regional distribution pattern was compared with location of γ-aminobutyric acid (GABA)ergic and glutamatergic cell groups, as identified by the expression of glutamic acid decarboxylase 65 (GAD65) and type 2 vesicular glutamate transporter (VGLUT2) mRNAs, respectively. The MS, DBB, and preoptic area showed overlaps between GABAergic and CB1-expressing neurons, whereas hypothalamic sites with moderate CB1 signals, including the LA, Pa, VMH, LM, and PMV, were dominated by glutamatergic neurons. Low CB1 mRNA levels were also present in other glutamatergic and GABAergic regions. Dual-label in situ hybridization experiments confirmed the cellular co-expression of CB1 with both glutamatergic and GABAergic markers. In this report we provide a detailed anatomical map of hypothalamic glutamatergic and GABAergic systems whose neurotransmitter release is controlled by retrograde endocannabinoid signaling from hypothalamic and extrahypothalamic target neurons. This neuroanatomical information contributes to an understanding of the role that the endocannabinoid system plays in the regulation of endocrine and metabolic functions.

Effects of Antidepressant Treatment on Sexual Arousal in Depressed Women: A Preliminary fMRI Study

OBJECTIVE: There was a recent study to explore the cerebral regions associated with sexual arousal in depressed women using functional magnetic resonance imaging (fMRI). The purpose of this neuroimaging study was to investigate the effects of antidepressant treatment on sexual arousal in depressed women. METHODS: Seven depressed women with sexual arousal dysfunction (mean age: 41.7+/-13.8, mean scores of the Beck Depression Inventory (BDI) and the 17-item Hamilton Rating Scale for Depression (HAMD-17): 35.6+/-7.1 and 34.9+/-3.1, respectively) and nine healthy women (mean age: 40.3+/-11.6) underwent fMRI before and after antidepressant treatment. The fMRI paradigm contrasted a 1 minute rest period viewing non-erotic film with 4 minutes of sexual stimulation viewing an erotic video film. Data were analyzed by SPM 2. The relative number of pixels activated in each period was used as an index of activation. All depressed women were treated with mirtazapine (mean dosage: 37.5 mg/day) for 8 to 10 weeks. RESULTS: Levels of brain activity during sexual arousal in depressed women significantly increased with antidepressant treatment (p<0.05) in the regions of the hypothalamus (3.0% to 11.2%), septal area (8.6% to 27.8%) and parahippocampal gyrus (5.8% to 14.6%). Self-reported sexual arousal during visual sexual stimulation also significantly increased post-treatment, and severity of depressive symptoms improved, as measured by the BDI and HAMD-17 (p<0.05). CONCLUSION: These results show that sexual arousal dysfunction of depressed women may improve after treatment of depression, and that this improvement is associated with increased activation of the hypothalamus, septal area, and parahippocampal gyrus during sexual arousal.

Transcriptional responses of the nerve agent-sensitive brain regions amygdala, hippocampus, piriform cortex, septum, and thalamus following exposure to the organophosphonate anticholinesterase sarin.

BACKGROUND: Although the acute toxicity of organophosphorus nerve agents is known to result from acetylcholinesterase inhibition, the molecular mechanisms involved in the development of neuropathology following nerve agent-induced seizure are not well understood. To help determine these pathways, we previously used microarray analysis to identify gene expression changes in the rat piriform cortex, a region of the rat brain sensitive to nerve agent exposure, over a 24-h time period following sarin-induced seizure. We found significant differences in gene expression profiles and identified secondary responses that potentially lead to brain injury and cell death. To advance our understanding of the molecular mechanisms involved in sarin-induced toxicity, we analyzed gene expression changes in four other areas of the rat brain known to be affected by nerve agent-induced seizure (amygdala, hippocampus, septum, and thalamus). METHODS: We compared the transcriptional response of these four brain regions to sarin-induced seizure with the response previously characterized in the piriform cortex. In this study, rats were challenged with 1.0 × LD50 sarin and subsequently treated with atropine sulfate, 2-pyridine aldoxime methylchloride, and diazepam. The four brain regions were collected at 0.25, 1, 3, 6, and 24 h after seizure onset, and total RNA was processed for microarray analysis. RESULTS: Principal component analysis identified brain region and time following seizure onset as major sources of variability within the dataset. Analysis of variance identified genes significantly changed following sarin-induced seizure, and gene ontology analysis identified biological pathways, functions, and networks of genes significantly affected by sarin-induced seizure over the 24-h time course. Many of the molecular functions and pathways identified as being most significant across all of the brain regions were indicative of an inflammatory response. There were also a number of molecular responses that were unique for each brain region, with the thalamus having the most distinct response to nerve agent-induced seizure. CONCLUSIONS: Identifying the molecular mechanisms involved in sarin-induced neurotoxicity in these sensitive brain regions will facilitate the development of novel therapeutics that can potentially provide broad-spectrum protection in five areas of the central nervous system known to be damaged by nerve agent-induced seizure.

Kindling of the lateral septum and the amygdala: effects on anxiety in rats.

Long-term kindling of limbic system structures may produce substantial changes in emotional behavior in rats. This study examined long-term changes in two kindled structures that have opposite effects on anxiety, the lateral septum and the central nucleus of the amygdala. The purpose of the experiment was to examine the specificity of the emotional effects of kindling by employing a double dissociation design. Animals were tested in two common animal models of anxiety, the water-lick conflict test and the elevated plus-maze. In the conflict test amygdala-kindled animals demonstrated a significant anxiolytic effect when compared with sham-kindled animals. This effect was potentiated by chlordiazepoxide. Septally-kindled animals exhibited a significant anticonflict effect when compared to sham-kindled animals in the first session. Septally-kindled animals spent significantly more time on the open arms of the elevated plus-maze than did sham-kindled animals. Observed changes persisted 6weeks after the termination of 150 kindling sessions. The effects of long-term kindling were highly consistent with those of disruption rather than facilitation.

Entrainment for distinguishing atypical atrioventricular node reentrant tachycardia from atrioventricular reentrant tachycardia over septal accessory pathways with long-RP [corrected] tachycardia.

BACKGROUND: The response to right ventricular (RV) entrainment is useful to distinguish atypical AV node reentrant tachycardia from AV reentrant tachycardia using a septal accessory pathway. Whether entrainment can differentiate between AV node reentrant tachycardia and AV reentrant tachycardia in patients with long-RP tachycardia has not been systematically validated. METHODS AND RESULTS: Twenty-four patients with concealed septal accessory pathways who had an electrophysiology study between January 1, 2000, and January 1, 2010, were included (age, 38 ± 17 years; men, 17). Entrainment was performed from the RV apex pacing at cycle length 20 to 40 ms shorter than tachycardia cycle length (TCL). The mean TCL was 390 ± 80 ms, the mean AH interval during tachycardia was 151 ± 57 ms, and the mean ventriculoatrial (VA) time was 182 ± 103 ms. Twelve patients had typical accessory pathways (VA/TCL <40%), and 12 had slowly conducting accessory pathways (VA/TCL ≥ 40%). In all patients with typical accessory pathways, the postpacing interval minus the TCL (PPI-TCL) was <115 ms and the difference in the VA interval during pacing and tachycardia (StimA-VA) was <85 ms. On the other hand, in 6 of the 12 patients in the slowly conducting group, the PPI-TCL was >115 ms, and the StimA-VA was > 85 ms. CONCLUSIONS: Slowly conducting accessory pathways frequently yield RV entrainment criteria traditionally attributable to AV node reentry. Distinguishing AV node reentry from AV reentry in patients with long-RP tachycardia requires other criteria.

Neural inputs of the hypothalamic "aggression area" in the rat.

A part of the mediobasal hypothalamus (known as hypothalamic attack area) plays a central role in the control of aggressive behavior as its electrical stimulation reliably and rapidly elicits biting attacks in cats and rodents. The efferent connections of this brain region were described in rats, but afferent pathways were not investigated so far. We injected the retrograde tracer cholera toxin B subunit into the mediobasal hypothalamus of male Wistar rats and studied the distribution of labeled cells by immunohistochemical method. The retrograde labeling outlined three continuous, distinct afferent cell populations: (i) a telencephalic midline "plate" containing the orbitofrontal - medial prefrontal - septal regions which ends in the bed nucleus of stria terminalis; (ii) a temporal column including the medial amygdala, amigdalohippocampal area and subiculum; (iii) a diffuse column along the medial hypothalamus which ends in the posterior hypothalamic nucleus. Sparse labeling was present in brainstem nuclei, except for the lateral parabrachial nucleus that provides a significant input. The projections of the medial prefrontal cortex to the hypothalamic attack area indicate a direct, earlier undescribed pathway with marked importance in the control of aggressive behavior. Similarly, we identified several brain regions which send very significant projections to the hypothalamic attack area but their importance in the control of aggressive behavior are nearly unknown. The comparison of the present and earlier findings shows that efferent and afferent connections overlap in many regions to a significant extent, suggesting that reverberating circuits are important in the control of aggressive behavior.