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PubMed2004

[The expression of Smac and XIAP in rat hippocampus following limbic seizure induced by kainic acid injection into amygdaloid nucleus].

To determine whether Smac/DIABLO (second mitochondrial activator of caspases/direct inhibitor of apoptosis protein-binding protein of low isoelectric point [PI]) and XIAP (X-chromosome-linked inhibitor of apoptosis protein) serve to regulate neuronal apoptosis following seizures, we investigated seizure-induced changes in caspase-9, Smac/DIABLO and XIAP protein expression and the in vivo effect of caspase-9 inhibition. Animals received unilateral intra-amygdaloid injection of kainic acid (0.5 microg) to induce seizures for 1 h. The seizures were then terminated by diazepam (30 mg/kg). Animals were killed 0, 2, 4, 8, 24 or 72 h following diazepam administration. The apoptotic and surviving neurons in hippocampus were observed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and cresyl violet staining, the expression of Smac/DIABLO, XIAP and caspase-9 was detected with immunofluorescence and western blot. The results showed that the levels of XIAP and the 46-kDa proenzyme form of caspase-9 were unaffected by the seizures. The expression of Smac increased at 2 h and the 37-kD cleaved fragment of caspase-9 was detected at 4 h, TUNEL-positive neurons appeared at 8 h and reached maximal at 24 h following seizure cessation within the ipsilateral (the same side as the intra-amygdaloid injection of kainic acid) CA3 subfield of the hippocampus. Intracerebroventricular infusion of caspase-9 inhibitor z-LEHD-fluoromethyl ketone (z-LEHD-fmk) significantly decreased TUNEL-positive neurons and increased the number of surviving cells. Caspase-9 immunoreactivity increased and Smac/DIABLO, XIAP immunoreactivity became extensive within the ipsilateral CA3 neurons. TUNEL-positive neurons and the alterations of the expression of Smac/DIABLO and XIAP within the ipsilateral CA3 were not detected within the contralateral hippocampus. These results suggest that seizures lead the translocation of Smac/DIABLO into the cytosol, the activation of caspase-9 and the change of subcellular locoalization of XIAP. These changes may play a role in the brain damage induced by seizures. Caspase-9 is possibly a potential therapeutic target in the treatment of brain injury associated with seizures.

Amygdala↗
PubMed1996

Projection neurons of the lateral amygdaloid nucleus are virtually silent throughout the sleep--waking cycle.

1. Amygdala neurons were recorded extracellularly during the sleep-waking cycle in chronically implanted cats. Neurons were identified as projection cells when they could be antidromically invaded from the perirhinal and/or entorhinal cortices. 2. In contrast with other nuclei of the amygdala, few spontaneously active neurons were encountered in the lateral nucleus. However, when hunting stimuli were applied to the parahippocampal cortices, we noticed the presence of numerous projection cells that would have otherwise remained undetected because they had little or no spontaneous activity. 3. In the states of waking, slow-wave sleep, and paradoxical sleep, the discharge rate of antidromically invaded neurons averaged 0.09 +/- 0.07 Hz (mean +/- SE) with 82% of cells firing at < 0.01 Hz in all states. However, they transiently increased their firing rate when cats were presented complex sensory stimuli, which apparently were specific to each cell. In contrast to projection cells, spontaneously active neurons of the lateral nucleus that could not be backfired from the parahippocampal cortices had an average firing rate of 4.34 +/- 1.15 Hz with 38% of cells firing at > or = 6 Hz in at least one state. 4. These results on the extremely low firing rates of identified projection cells suggest that previous extracellular studies of lateral amygdaloid neurons were biased toward a class of spontaneously active cells which probably includes local-circuit cells.

Amygdala↗
PubMed1983

Do amygdaloid nucleus centralis and nucleus lateralis serve similar functions in defensive responding in cats?

Bar pressing escape response has been trained, extinguished, retrained and then transformed into avoidance response in cats subjected to electrocoagulation of either the dorsolateral part of the central nucleus (Group CE) ox the lateral nucleus (Group L) of amygdala. In comparison with normal carts Group L was deficient in acquisition of the short latency escape responses and Group CE was handicapped in reacquisition of the escape response after the extinction procedure. Both lesioned groups were unable to acquire avoidance responding. Group CE was marked by gradual decrease of the sensitivity to shock in the course of learning, whereas Group L was less sensitive to changes in experimental procedures than the other two groups. However, most of the observed group differences were related to a decrease of sensitivity to shock and to a lowered general emotionality produced by lesions in both amygdaloid nuclei.

Aggression↗
PubMed1984

The cortical projection of the basolateral amygdaloid nucleus in the rat: a retrograde fluorescent dye study.

The fluorescent dye, retrograde labeling technique was used to determine the extent of the projection from the basolateral nucleus of the amygdala to the neocortex in the rat. Each rat received a single cortical injection of fast blue, and in one-half of the animals, a subsequent injection of nuclear yellow was placed in a different cortical region. An analysis of the results demonstrates that the projection to the midline cortex arises in the medial neurons within the caudal two-thirds of the basolateral nucleus. This projection is directed to the anterior cingulate cortex, but not to the posterior cingulate cortex. The primary motor cortex receives a basolateral amygdala projection which originates from neurons in two areas, (1) the medial part of the anterior one-third of the nucleus and (2) the center (in the lateral to medial axis) portion of the posterior two-thirds of the nucleus. The latter neurons are situated lateral to the neurons projecting to the cingulate cortex. Somatosensory cortex injections label many fewer basolateral nucleus neurons than do motor cortex injections, but these neurons are located in a position similar to that of those labeled by motor cortex injections. Finally the gustatory cortex, which lies just dorsal to the rhinal sulcus, receives a basolateral projection from neurons in the lateroventral one-half of the basolateral nucleus. These results demonstrate that the basolateral nucleus gives rise to a rather widespread and topographically organized projection to the anterior half of the neocortex of the rat.

Amidines↗
PubMed1982

Antinociception after microinjection of neurotensin into the central amygdaloid nucleus of the rat.

Neurotensin (NT) is an endogenous peptide which has been hypothesized to function in the central nervous systems as a neurotransmitter. Injection of NT into the cerebral ventricular system of rodents produces antinociception in a variety of analgesia tests. In the hot plate test, direct microinjection of NT into the central nucleus of the amygdala (AC) produced a significant increase in the nociceptive threshold of the rat, while injections into tissue adjacent to the AC were generally ineffective. Antinociception following intra-AC injection of NT occurred at an ED50 dose of 2.4 micrograms NT, and was significantly lower than the ED50 dose observed when NT was given into the lateral ventricles (93.2 micrograms NT). Lesions of the stria terminalis totally abolished the antinociceptive effect of intra-AC administration of NT, indicating that AC efferent or afferent fibers within the stria terminalis are necessary for the observed increase in nociceptive threshold.

Amygdala↗
PubMed1986

The human medial amygdaloid nucleus: no evidence for sex difference in volume.

The volume of the medial nucleus of the amygdala was determined in the right and in the left hemispheres in 17 human brains ranging in age from 35 weeks of gestation to 94 years of age. An analysis of covariance which adjusted for differing age and brain size distributions in the male and female samples showed no significant sexual dimorphism in medial nucleus volume. This finding is discussed in relation to evidence for sexual dimorphism in the medial nucleus of the amygdala in animal brains.

Adolescent↗
PubMed1992

Glutamate immunoreactive terminals in the lateral amygdaloid nucleus: a possible substrate for emotional memory.

The ultrastructure and synaptic associations of terminals immunoreactive for L-glutamate (Glu) were examined in the lateral nucleus of the amygdala (AL). All results reported here involved tissue fixed only with paraformaldehyde. The specificity of the antiserum with paraformaldehyde fixation conditions was assessed and confirmed by immuno-dot blot analysis: the reactivity of anti-Glu to glutamic acid was at least 1,000 times greater than the reactivity to other amino acids. At the light microscopic level, Glu-immunoreactive punctate processes and somata were present in AL. At the electron microscopic level, many Glu-immunoreactive terminals were identified. Data analysis was performed on 365 of these labeled terminals. Glu-immunoreactive terminals were 0.3-1.5 microns in diameter and contained numerous small, clear vesicles as well as mitochondria. Many (77%) of the terminals analyzed had morphologically identifiable synaptic specializations. Most (90%) of the Glu-immunoreactive terminals with synaptic specializations formed asymmetric synapses on spines or small dendrites; synaptic specializations on soma or proximal dendrites were rarely seen (< 1%). Glu-immunoreactive terminals were qualitatively compared to terminals in AL labeled with two other antisera: anti-glutaminase, a marker for the enzyme that catalyzes the conversion of glutamine to the releasable or transmitter form of Glu, and anti-gamma-aminobutyric acid (anti-GABA), a marker for the major inhibitory amino acid transmitter in the brain. Terminals immunoreactive for glutaminase, like those immunoreactive for Glu, formed mostly asymmetric synaptic specializations on spines or small dendrites. In contrast, GABA-immunoreactive terminals usually formed symmetric synapses on soma or proximal dendrites and were never observed to form asymmetric axo-spinous contacts. Although Glu is a metabolic precursor to GABA, these data indicate that the majority of Glu-immunoreactive terminals reflect the site of synthesis and release of Glu and not of GABA. In addition, these results provide morphological evidence that Glu plays a role in excitatory neurotransmission at synapses in AL and support the growing body of data implicating excitatory amino acid-mediated synaptic plasticity in-emotional learning and memory processes in AL.

Amino Acids↗
PubMed1996

Dentate gyrus field potentials evoked by stimulation of the basolateral amygdaloid nucleus in anesthetized rats.

We previously found that long-term potentiation (LTP) in the dentate gyrus (DG) is attenuated by lesion of the basolateral amygdala (BLA), but it remained unclear whether or not there is neural connection between the BLA and the DG. In the present study, we tried to provide physiological evidence that the DG receives neural inputs from the BLA. Single-pulse electrical stimulation of the BLA evoked two distinct components of field potentials in the ipsilateral DG: the P1 component with 26-ms peak latency was elicited by lower intensity of BLA stimulation, whereas the P2 component with 14-ms peak latency was elicited at higher stimulus intensity. The PI response (1) was evoked when the stimulating electrode was positioned within the BLA, (2) showed the laminar profile similar to the perforant path (PP)-evoked response and (3) exhibited strong paired-pulse facilitation. On the other hand, the P2 wave (1) was evoked even with the stimulating electrode outside the BLA, (2) did not reverse its polarity at any location in the DG and (3) showed only slight facilitation by paired-pulse stimulation. These data indicate that the P1 component represents synaptic responses of DG granule cells to neural inputs from the BLA. Furthermore, the BLA-evoked DG field potentials were not affected by local injection of tetracaine into the PP and displayed LTP independently of the PP-evoked response, suggesting that neural inputs from the BLA are not mediated by the PP.

Amygdala↗
PubMed1984

The rat amygdaloid nucleus: a morphometric right-left study.

Our results indicate that Long-Evans male rats housed in standard conditions show no significant difference between the areas of sections of their left and right amygdalas. In contrast, the S1 strain maze-bright animals have a significantly greater right amygdala than left. Furthermore, the data indicate an overall increase in mean (R + L)/2 amygdala area from 6 to 400 days, except for a significant decrease in area from 26 to 90 days.

Aging↗
PubMedDate not supplied

Organization and interrelationship of neuropeptides in the central amygdaloid nucleus of the rat.

The organization and interactions of neuropeptides in the central nucleus of the amygdala (Ce) were studied using single and double label immunocytochemical techniques. Immunocytochemical localization of substance P (SP), neurotensin (NT), met-enkephalin (m-ENK), somatostatin (SS) and vasoactive intestinal polypeptide (VIP) revealed all of these peptides within discrete regions of the Ce. The regions differed from the classical medial and lateral anatomical divisions reported for the Ce. Instead, three easily recognizable neuropeptidergic subdivisions were evident: a medial zone, a central zone and a lateral capsular zone. Two types of interrelationships between peptides were noted. The first involved a peptidergic fiber in apposition to a peptidergic perikarya. The most prevalent peptidergic interaction of this type occurred between SP and NT. The second interrelationship involved two different peptidergic fibers in apposition to an immunonegative cell. Two interactions of this type were commonly observed. The first involved NT and m-ENK fibers simultaneously apposed to an unstained cell. The second involved SP and m-ENK fibers adjacent to the same immunonegative cell. The interactions between peptidergic systems may suggest a role of these substances in the regulation of autonomic functions in the Ce.

Amygdala↗
PubMed1989

The central amygdaloid nucleus innervation of the dorsal vagal complex in rat: a Phaseolus vulgaris leucoagglutinin lectin anterograde tracing study.

The central nucleus of amygdala (Ce) participates in expression of autonomic responses associated with fear or stress-related behaviors. The Ce can alter autonomic activity through its direct projection to the dorsal vagal complex [i.e., nucleus of the solitary tract (nTS) and the dorsal vagal nucleus]. In order to more precisely define the anatomical organization of the neurons within the Ce and their terminal fields within the dorsal vagal complex, the Phaseolus vulgaris leucoagglutinin lectin (PHA-L) anterograde tracing method was employed in rats. In cases where injections of PHA-L were centered within the medial Ce, dense axon terminal labeling was observed within the medial nTS at rostral levels. Terminal boutons were also observed within the ventral part of the lateral nTS, the dorsal vagal nucleus and contralateral medial nTS. At and just rostral to the obex, numerous axonal boutons were seen within the medial and commissural parts of the nTS and adjacent parts of the dorsal vagal nucleus. Contralateral axon terminal labeling was present within the medial and commissural parts of the nTS. Caudal to the obex, PHA-L immunoreactive boutons were concentrated bilaterally within the medial and commissural nTS and dorsal vagal nucleus. In cases where injections of PHA-L were centered within the lateral Ce moderate axon terminal labeling was observed throughout the rostrocaudal extent of the medial and commissural part of the nTS. Very few PHA-L immunoreactive terminals were observed within the ventral part of the lateral nTS, dorsal vagal nucleus and contralateral medial nTS. The results demonstrate that the medial Ce projects bilaterally to the medial and commissural subnuclei of the nTS and the dorsal vagal nucleus. The lateral Ce projects mainly to the ipsilateral medial and commissural nTS. Thus, both the medial and lateral Ce can directly influence regions of the nTS where peripheral cardiovascular, cardiopulmonary and gastric afferents terminate. The medial Ce can also directly affect vagal nerve outflow through its projection to neurons within the dorsal motor nucleus.

Amygdala↗