An analysis of the mechanisms underlying septal area control of hypothalamically elicited aggression in the cat

This experiment was performed in order to examine several of the underlying mechanisms by which the septal area and adjacent regions regulate quiet biting attack behavior elicited from electrical stimulation of the hypothalamus in the cat. The results clearly indicate that stimulation of the septal area and anterior cingulate gyrus increased the latency for the occurrence of quiet biting attack behavior. Those sites within the septal area from which inhibition of attack can be produced are linked to sensory mechanisms associated with trigeminal reflexes activated during hypothalamic stimulation. Stimulation of these septal area sites decreased the lateral extent of the ‘effective sensory fields’ of the lipline established during hypothalamic stimulation, but did not appear to have any affect upon] the latency of the hypothalamically elicited jaw-opening response. Deoxyglucose autoradiography revealed that the inhibition resulting from stimulation of the lateral septal area may be due to either the monosynaptic activation of the lateral hypothalamus or the disynaptic activation of this area utilizing a circuit involving the nuclei of the diagonal band of Broca.     

Effects of amygdaloid stimulation upon trigeminal sensory fields of the LIP that are established during hypothalamically-elicited quiet biting attack in the cat

An experiment was performed in order to determine the role of the amygdala and surrounding cortex in quiet biting attack elicited from electrical stimulation of the hypothalamus. Stimulation of basal, cortical, and anterior amygdala as well as pyriform cortex and parahippocampal gyrus resulted in a suppression of the attack response and in a constriction of trigeminal sensory fields that are established during hypothalamic stimulation. Stimulation of lateral and central amygdala resulted in a facilitation of the quiet biting attack response and an expansion of the trigeminal sensory fields, and a decreased latency for the occurrence of jaw opening when the sensory field was held constant. These studies suggest that the amygdala modulated quiet biting attack behavior generated by hypothalamic stimulation at least, in part, by virtue of its control over sensory fields.     

The pathways mediating affective defense and quiet biting attack behavior from the midbrain central gray of the cat: an autoradiographic study

The purpose of this study was to describe the pathways which mediate feline affective defense and quiet biting attack behavior elicited from the midbrain central gray. In these experiments, methods of [3H]leucine and 2-deoxy-[14C]glucose (2-DG) radioautography were utilized in concert with the technique of electrical and chemical brain stimulation. Affective defense behavior elicited from the midbrain central gray is characterized by marked vocalization such as hissing and growling, pupillary dilatation, urination and piloerection. In contrast, quiet biting attack elicited from the midbrain central gray lacks overt autonomic signs observed with affective defense response as well as the stalking component which is typically associated with stimulation of the lateral hypothalamus. Nevertheless, central gray-elicited attack resulted in a directed bite of the neck of an anesthetized rat in a manner similar to that observed from the hypothalamus. Affective defense was elicited from the dorsal half of the midbrain central gray, while quiet biting attack was obtained following stimulation of the ventral half of the midbrain central gray, thus indicating a functional differentiation of the central gray with respect to these two forms of aggression. In a separate series of experiments, affective defense or quiet biting attack response was identified by electrical stimulation through a cannula electrode situated in the midbrain central gray. The affective defense responses were subsequently elicited following microinjections of D,L-homocysteic acid through the same cannula electrode in order to demonstrate that these responses were the result of direct stimulation of cell bodies within the central gray. Then, one of the following autoradiographic tracing procedures was utilized: (1) [3H]leucine was injected through a cannula electrode and the animal was sacrificed after a 4- to 14-day survival period; or (2) a 2-DG solution was systemically injected and electrical stimulation was applied through the cannula electrode in order to metabolically activate the pathways associated with each of these responses. In general, the pattern of labelled target regions as indicated by 3H-amino acid radioautography was similar to that obtained from the 2-DG autoradiographic analysis. The principal ascending pathway associated with affective defense was traced to the anteromedial hypothalamus and medial thalamus. Concerning descending projections, label was traced into the central tegmental fields of the midbrain and pons, locus coeruleus and motor and main sensory nuclei of the trigeminal complex.(ABSTRACT TRUNCATED AT 400 WORDS)     

The organization of the hypothalamic pathways mediating affective defense behavior in the cat

The purpose of this study was to describe the hypothalamic pathways which mediate affective defense in the cat utilizing the methods of [14C]2-deoxyglucose (2-DG) and [3H]leucine radioautography in concert with the technique of electrical brain stimulation. The feline affective defense response, characterized by pupillary dilatation, piloerection, ear retraction, hissing, growling and striking with the forepaws, was elicited consistently by stimulation of sites within the ventromedial hypothalamus and anterior aspect of the medial hypothalamus. In one series of experiments, 2-DG autoradiography was employed to describe the brain regions activated following stimulation of sites in the region of the ventromedial hypothalamus from which affective defense had been elicited. Ventromedial hypothalamic stimulation produced activation primarily in forebrain regions situated rostral to the level of the stimulating electrode. These structures included principally the anteromedial hypothalamus and medial preoptic area, as well as the bed nuclei of the stria terminalis and anterior commissure, diagonal band and lateral septal area. The caudal extent of activation included only the dorsal and perifornical hypothalamus at the level of the stimulation site. In a second series of experiments, affective defense sites in the anteromedial hypothalamus were stimulated and the regional distribution of 2-DG label was identified. In contrast to the results obtained from ventromedial hypothalamic stimulation, these experiments revealed a marked descending distribution of label within the posterior hypothalamus, midbrain central gray and ventral tegmental area. Results obtained from studies in which tritiated amino acids were injected into affective defense sites in both the ventromedial nucleus and anteromedial hypothalamus confirmed the general findings observed with 2-DG autoradiography. From these observations, we have concluded that the organization of the pathway mediating affective defense behavior from the ventromedial hypothalamus to the midbrain involves an initial synapse within the region of the anteromedial hypothalamus and a second synapse in the midbrain central gray substance. The significance of the anteromedial hypothalamus for the expression of affective defense behavior was considered in the Discussion.     

[C]2-Deoxyglucose demonstration of the organization of ocular dominance in areas 17 and 18 of the normal cat

The purpose of this study was to demonstrate the spatial organization of ocular dominance in the visual cortex of the cat. We administered [14C]2-deoxyglucose ([14C]2-DG) to 4 alert, monocularly stimulated cats; one eye had previously been removed from 3 of these cats, and the other cat had received a uniocular injection of tetrodotoxin (TTX). In areas 17 and 18, but not in area 19, we observed alternating regions of heavy and light label, which were clearest in layer IV. Near the representation of the area centralis, especially in the hemisphere ipsilateral to the stimulated eye, the labeled regions formed columns that extended from the pial surface to the white matter. In the representation of peripheral retina, especially in the hemisphere contralateral to the stimulated eye, the pattern was often (but not always) restricted to the middle layers. We conclude that this pattern of label reflects the organization of ocular dominance because: (1) we never observed this pattern in control cats in which both eyes were stimulated or neither eye was stimulated; (2) many characteristics of the pattern are consistent with physiological studies of ocular dominance, and (3) the width and spacing of the alternating label was consistent with the size of the patches of geniculocortical afferents representing the left and right eyes in layer IV of areas 17 and 18.     

Neural pathways mediating hypothalamically elicited flight behavior in the cat

This study has sought to identify hypothalamic pathways mediating flight behavior in the cat. Flight behavior, characterized by an initial pupillary dilatation and followed by vigorous attempts to leap out of the observation chamber, was elicited primarily by electrical stimulation of the medial preoptic region and dorsomedial hypothalamus, and to a lesser extent from the perifornical region. A [14C]-2-deoxyglucose analysis was utilized to examine brain regions functionally activated by stimulation of hypothalamic sites which elicited flight behavior. In a second series of experiments, [3H]leucine injected into regions surrounding electrode tips from which flight had previously been elicited, permitted identification of pathways arising from such functionally characterized sites. We describe for the first time pathways arising from the hypothalamus which mediate flight behavior. In spite of individual variation in placement of electrodes eliciting flight, a consistent pattern of labeling was observed following injection of either [14C]-2-deoxyglucose systemically or [3H]amino acids into the hypothalamus. The primary rostral target structures receiving inputs from flight electrode sites included the nuclei of the diagonal band, bed nucleus of the stria terminalis, medial amygdaloid nucleus, lateral septal nucleus, and anterior medial preoptico-hypothalamus. Caudal to the level of stimulation, the principal target nuclei involved the centrum medianum-parafascicular complex and the midbrain central gray substance. Possible roles of these nuclear regions in organization and regulation of flight behavior is discussed.     

The role of the anterior hypothalamus in affective defense behavior elicited from the ventromedial hypothalamus of the cat

In the preceding paper a hypothalamic circuit subserving feline affective defense behavior was described. This circuit included an ascending component from the ventromedial nucleus to the anterior hypothalamus and a descending component from the anterior hypothalamus to the midbrain central gray substance. The present study was undertaken to test the hypothesis that the anterior hypothalamus plays a central role in the organization of this functional pathway. In the first part of this study, dual stimulation methods were utilized to demonstrate that concurrent stimulation of the ventromedial hypothalamus facilitates the occurrence of affective defense responses elicited from the anterior hypothalamus. In the second part of the study, lesions placed in the anterior hypothalamus significantly increased the latency and threshold current for affective defense responses elicited from the ventromedial hypothalamus. [14C]2-deoxyglucose autoradiography confirmed the fact that anterior hypothalamic lesions effective in blocking affective defense were placed in regions where the vast majority of ventromedial hypothalamic fibers terminate. In contrast, lesions which had little or no effect upon the latency or threshold for affective defense elicited from the ventromedial hypothalamus appeared to leave intact the connections from the ventromedial to the anterior hypothalamus. These findings are consistent with the proposed intrahypothalamic anatomical substrate subserving affective defense behavior described in the preceding paper.     

Cerebral and local cerebral metabolism in the cat during slow wave and REM sleep

[14C]2-deoxyglucose autoradiography was used to show cerebral and regional cerebral metabolism during slow-wave sleep (SWS) and rapid-eye-movement sleep (REM) in the cat. Lower levels of mean cerebral metabolism, reflecting cerebral energy conservation, were associated with SWS. A clear link between REM and mean cerebral metabolism was not observed. At the regional level, SWS was associated with markedly low metabolism in thalamic sensory relays and in cortex. REM was associated with relatively low metabolism in the cerebellum, but with relatively high metabolism in the hippocampus, and in some 'motor' regions including the trigeminal and red nuclei. Thus, SWS was linked to cerebral energy conservation and to particularly low levels of functional activity in cortical and sub-cortical sensory regions. REM was unlike SWS in that: REM did not appear to be strongly linked to cerebral energy conservation; REM was linked to metabolism in fewer brain regions than was SWS; and most REM-linked regions exhibited relatively high levels of metabolism. In addition, while SWS was most clearly associated with functional activity in sensory regions, REM was linked to functional activity in a small number of limbic and motor regions. In sum, SWS and REM are associated with distinctive cerebral metabolic and functional states.     

Global increase in cerebral metabolism and blood flow produced by focal electrical stimulation of dorsal medullary reticular formation in rat

We sought to determine whether the increases in local cerebral blood flow (LBCF) elicited by focal electrical stimulation within the dorsal medullary reticular formation (DMRF), are secondary to or independent of, increased local cerebral glucose utilization (LCGU).Rats were anesthetized (chloralose), paralyzed, artificially ventilated and arterial pressure and blood gases controlled. LCBF and LCGU were determined in two separate groups of animals, using the autoradiographic [¹⁴C]iodoantipyrine and [¹⁴C]2-deoxyglucose methods, respectively. In unstimulated controls, LCBF (n= 5) and LCGU (n= 5) were linearly related (r = 0.780; P < 0.001) in the 27 brain regions studied. During DMRF stimulation LCGU increased significantly in 21 of the 27 regions, including cerebral cortex (up to 168% of control), thalamic nuclei (up to 161%) and selected ponto-medullary regions (e.g. parabrachial complex: 212%; vestibular complex: 147%). Along with LCGU, LCBF rose significantly in 25 regions (sensory motor cortex: 163%; anterior thalamus: 161%; parabrachial complex: 186%). Correlation analysis demonstrated that, during DMRF stimulation, the close relationship between LCBF and LCGU is preserved (r = 0.845; P < 0.001) and that, in addition, the increase in LCBF (δ LCBF) is proportional to the increase in LCGU (δ LCGU) (δLCGU+ 6.92; r = 0.7729; P < 0.001).Excitation of neurons or fibers within DMRF increases brain metabolism globally and blood flow secondarily. The DMRF appears to modulate cerebral metabolism globally, by as yet undefined pathways.     

Stimulus-dependent labeling of cultured ganglionic cell with [C]2-deoxyglucose

We prepared cultures of dissociated cells from the ciliary (CG) and dorsal root ganglion (DRG) of 10–12-day-old chick embryos, and applied [¹⁴C]2-deoxyglucose ([¹⁴C]2-DG) to the cultured cells to examine the effects of stimulation on the labeling with [¹⁴C]2-DG at the single cell level. Electrical current stimulation increased [¹⁴C]2-DG uptake in CG and DRG neurons. The increase depended on frequency of the stimulation. These effects were potentiated by the application of tetraethylammonium, but suppressed by tetrodotoxin. Externally applied potassium ions increased the [¹⁴C]2-DG uptake in the CG cell, depending logarithmically on the concentration of applied KC1. The concentration-dependent increase agreed with potassium effect on the equilibrium potential. For CG cells, acetylcholine (ACh), glutamate, γ-aminobutyric acid (GABA) and glycine induced remarkable increases of the [¹⁴C]2-DG uptake, while dopamine did not induce any change. For DRG cells, GABA and glycine facilitated the [¹⁴C]2-DG uptake, while ACh, glutamate and dopamine did not have any significant effects on it. These facilitatory actions of neurotransmitters on the [¹⁴C]2-DG uptake are mostly consistent with the excitatory effects of the substrates on both CG and DRG cells in culture. The results suggest that the [¹⁴C]2-DG uptake in single cells is intimately correlated with action potential generation and change in the resting potential.     

Topographically organized midbrain modulation of predatory and defensive aggression in the cat

Hypothalamic sites from which quiet biting attack and affective defense were elicited, were concurrently stimulated with others in the midbrain from which modulation of these behaviors was attempted. Stimulation of medial and lateral aspects of the tegmentum differentially modulated quiet biting attack and affective defense behavior. Facilitation of quiet attack and suppression of affective defense resulted from stimulation of the lateral tegmentum, while suppression of quiet attack and facilitation of affective defense followed stimulation of its medial aspect.     

Lateralized loss of biting attack-patterned reflexes following induction of contralateral sensory neglect in the cat: A possible role for the striatum in centrally elicited aggressive behaviour

A syndrome of ‘contralateral sensory neglect’ was induced by hypothalamic knife cuts in 6 of 10 cats in which quiet biting attack behaviour could be elicited by lateral hypothalamic stimulation. The contralateral sensory neglect in the 6 affected cats was accompanied by a loss on the ‘neglected’ side of the body of the patterned reflexes which mediate positioning of the head to bite and the jaw-opening component of biting. As a result, when these cats were stimulated in the lateral hypothalamus, although they continued to approach and even make tactile contact with the rat, they generally failed to bite it. Analysis of the histological and behavioural data suggested that damage to the nigrostriatal and/or striato/pallidonigral fibre systems provided the likely basis for both the induction of the contralateral sensory neglect and the lateralized patterned reflex loss. It was suggested, with respect to these specific patterned reflex components of the attack, that an important contribution may be made by the striatum.     

The effect of auditory stimulus rate on [C]2-deoxyglucose uptake in rabbit inferior colliculus

The relationship between auditory stimulus rate and level of [¹⁴C]2-deoxyglucose (2-DG) uptake was examined using the 2-DG technique developed by Sokoloff³⁴ as an indication of glucose uptake and neural activity. Conscious restrained albino rabbits were given one monaural tone either once per second or once per minute for 45 min, or served as unstimulated controls. Autoradiographs of the inferior colliculi from these animals were compared densitometrically. It was found that the rabbits stimulated once per second had markedly elevated levels of 2-DG uptake compared to both other groups: the rabbits stimulated once per minute and to unstimulated control rabbits. In addition, the inferior colliculus autoradiographs of the rabbits stimulated with pure tones showed a distinctive banding pattern in central nucleus different from that seen in control rabbits.     

Metabolic mapping of the rat brain involved in thermoregulatory responses using the [C]2-deoxyglucose technique

The central nervous structures involved in thermoregulatory responses to thermal stimulation of the preoptic/anterior hypothalamic region were investigated in conscious, unrestrained rats by means of the 2-deoxy-d-[¹⁴C]glucose autoradiographic technique. Significant activation in metabolic activity was observed in the medial preoptic area, medial forebrain bundle, anterior part of ventromedial hypothalamus, anteroventral thalamus, dorsomedial thalamus, basal ganglia, pars compacta of substantia nigra, red nucleus and the reticular formation.     

Focal and diffuse metabolic changes in the spinal cord of the monkey elicited by microstimulation of differing motor cortical foci

The pattern of projections from identified motor cortical efferent zones onto the spinal cord was examined in the monkey using a combination of microstimulation and [14C]2-deoxyglucose metabolic labeling. Regional differences were found in the branching patterns between the projections of proximal and distal forelimb foci of the motor cortex onto the spinal cord. Cortical efferent zones related to proximal movements project extensively within the spinal cord activating numerous motor nuclei. In contrast, the corticospinal projection of a distal movement zone was found to be significantly more restricted in overall rostrocaudal extent projecting with greatest density onto a small focal region of the ventrolateral horn.     

Acute administration of high doses of estrogen increases glucose utilization throughout brain

The effects of high intravenous doses of estradiol benzoate on local cerebral glucose utilization were studied by the [14C]2-deoxyglucose method in conscious ovariectomized adult rats. Statistically significant increases in glucose utilization averaging 20% were observed in 42 of 60 anatomically discrete regions of the estrogen-treated animals. The possible role of catechol estrogen, a potent inhibitor of catechol-O-methyltransferase, in these effects is considered.     

Resolution-limiting factors in 2-deoxyglucose autoradiography. I. Factors other than Diffusion

We measured the extent to which factors other than the diffusion of the radioactive label during tissue preparation limits the spatial resolving power of 2-deoxyglucose (2-DG) autoradiography. Radioactive swept frequency gratings were created using microcircuit lithography. The gratings consisted of alternating equal width radioactive and non-radioactive bars in groups of narrowing bar width (effective range 500-20 μm). The vertical thickness of the gratings ranged from 2.25 to 20 μm. The isotope in the radioactive bars was either¹⁴C or³H. A variety of X-ray films were exposed to these gratings and the resulting images scanned with microdensitometers or video digitizers to determine the fall oof in image contrast (dark-bar values minus light-bar values) as a function of the number of dark bars (lines) per millimeter. The power of the isotope was the resolution limiting factor. Grating thickness and type of film made little difference. The limit of resolution with¹⁴C was 10 lines/mm; with³H, it was 25 lines/mm. The microdensitometer itself is apt to be a resolution limiting factor; the resolving power of those commonly used in autoradiography is unlikely to exceed 10 lines/mm. From measurements of the steepness of gray-matter to white-matter transitions in the image from a tissue section, we conclude that the resolution in the image is no worse than 1.6–3.2 lines/mm. Either the isotope or diffusion of the 2-DG during tissue preparation must be the factor that limits resolution.     

On the mechanism of enhanced release of [C]glutamate in hippocampal long-term potentiation

K⁺-induced release of [¹⁴C]glutamate was studied in slices of dentate gyrus prepared from control rats and rats in which long-term potentiation (LTP) had been induced in vivo. At all concentrations of Ca²⁺ studied, release from potentiated slices was greater than from control slices. In the same preparations both Ruthenium Red and caffeine enhanced basal release but in potentiated tissue the Ruthenium Red-induced release was significantly greater than in control tissue. These results are discussed in the light of our recent finding that enhanced transmitter release is associated with LTP.