Effects of stimulation of the substantia innominata upon attack behavior elicited from the hypothalamus in the cat

Experiments were undertaken in order to determine the role of the substantia innominata and surrounding regions in quiet biting attack elicited from electrical stimulation of the hypothalamus in the cat. Stimulation from sites in the lateral aspect of the substantia innominata resulted in a suppression of quiet biting attack and in a constriction of the 'effective trigeminal sensory fields' established during hypothalamic attack site stimulation. Stimulation from sites situated more medially in the substantia innominata resulted in a facilitation of quiet biting attack and in an expansion of the 'effective trigeminal sensory fields'. The motor component of the jaw opening response was altered in only 50% of the cases in contrast to the consistent effects observed upon the 'effective sensory fields'. Electrical stimulation of the substantia innominata had little effect upon affective display elicited from the ventromedial hypothalamus. Stimulation from sites located in the nucleus accumbens had no effect upon hypothalamically-elicited quiet biting attack and inhibited the occurrence of affective display in 2 to 5 animals tested. These studied suggest that the substantia innominata differentially modulates quiet biting attack and accomplishes this, at least in part, through its effects upon sensory mechanisms associated with the jaw opening reflex.     

Role of the limbic system in hypothalamically elicited attack behavior

The present review summarizes our research findings concerning the role of the limbic system in hypothalamically-elicited aggression in the cat. Utilizing a dual-stimulation procedure, our results indicate that much of the limbic system suppresses quiet biting attack behavior. The most potent inhibitory effects were obtained from the basomedial amygdala and the prefrontal cortex. Other structures displaying suppression of attack following electrical stimulation include the dorsal hippocampus, pyriform cortex, lateral septal nucleus, lateral aspect of substantia innominata, and anterior cingulate gyrus. Sites producing facilitation of attack include the ventral hippocampus, far lateral aspect of the lateral septal nucleus, medial aspect of the substantia innominata, and lateral amygdaloid nucleus. Anatomical studies suggest that the medial forebrain bundle and stria terminalis are utilized by limbic structures to provide direct modulation of the hypothalamus while the substantia innominata, mediodorsal thalamic nucleus and bed nucleus of the stria terminalis contain important interneurons in the control of quiet biting attack. Further studies indicate that the amygdala, ventral hippocampus, and substantia innominata may control aggressive behavior by modulating the trigeminal sensory components of the attack response.     

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.     

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)     

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.     

Effects of electrical stimulation of the lateral aspect of the prefrontal cortex upon attack behavior in cats.

An experiment was performed to determine the role of the lateral aspect of the prefrontal cortex upon quiet biting attack behavior elicited from the hypothalamus in the cat. The results of this experiment indicate that stimulation of 19 of 28 electrode sites sampled in the lateral prefrontal cortex produced a statistically significant inhibition of attack behavior elicited from the hypothalamus of the ipsilateral side. Stimulation of sites in the prefrontal cortex on the side contralateral to the hypothalamus from which attack was elicited had no effect upon this response. No systematic effect of prefrontal stimulation upon flight behavior was observed. Anatomical studies suggest that the lateral prefrontal cortex may inhibit attack behavior by modulating neurons in either the mediodorsal thalamic nucleus or ventral tegmental area.     

A [C]2-Deoxyglucose analysis of the functional neural pathways of the limbic forebrain in the rat. III. The hippocampal formation

The regions metabolically activated in the rat brain following focal electrical stimulation of various components of the hippocampal formation were identified with the use of [¹⁴C]2-deoxyglucose (2-DG) autoradiography. The results of these experiments, conducted in the rat, showed that in the absence of elicited afterdischarge activity, stimulation of either the CA1 or CA3 field of the dorsal hippocampus resulted in bilateral metabolic activation of only the dorsal hippocampus as well as of a relatively restricted region within the dorsomedial aspect of the lateral septal nucleus, bilaterally. In contrast, stimulation of either the CA1 or CA3 field of the ventral hippocampus resulted in bilateral activation of the ventral hippocampus and no region of the dorsal hippocampus. Following such stimulation, the lateral septal nucleus was also labeled bilaterally, but the activated regions were situated in a position ventrolateral to those resulting from stimulation at dorsal levels. Stimulation of the subicular cortex, in contrast, resulted in only ipsilateral activation of the hippocampal formation and lateral septal nucleus. Further rostral levels of the lateral septal nucleus were noted to be activated following stimulation of subicular cortex as compared to stimulation of the cornu Ammonis.The hypothalamus was directly activated by two pathways, the postcommissural fornix and the medial corticohypothalamic tract. Following stimulation at dorsal and posterior levels of CA1 and the subiculum, the mammillary bodies were demonstrably labeled by input from the postcommissural fornix. Regions of the medial hypothalamus were activated via the medial corticohypothalamic tract following stimulation of the ventral subiculum.The amygdala, stria terminalis and its bed nucleus were also shown to be demonstrably activated following stimulation of the ventral subiculum, ventral CAl field and posterior prosubiculum. This pathway may represent an additional route by which hippocampal modulation may indirectly modulate hypothalamic function.The presence of elicited afterdischarges resulted in more extensive patterns of metabolic labeling within the hippocampal formation and lateral septal nuclei as compared to experiments in which afterdischarges were not elicited. The extent of the demonstrable labeling, both within, and extrinsic to the hippocampal formation appeared to be a function of the duration and severity of the elicited seizure discharge. Additional structures which were demonstrably labeled following the elicitation of seizure activity include the entorhinal cortex-prepyriform area, amygdala, substantia innominata, putamen, substantia nigra, olfactory and prefrontal cortices and medial thalamic nuclei.     

Identification of neuronal cell bodies mediating components of biting attack behaviour in the cat: induction of jaw opening following microinjections of glutamate into hypothalamus

Microinjections of glutamic acid were made into the same hypothalamic and midbrain sites at which a biting attack of a cat upon a rat was elicited by electrical stimulation. It was found that: (1) caudal lateral hypothalamic and ventral midbrain tegmental glutamate injections were without behavioural effects; and (2) perifornical hypothalamic glutamate injections elicited the jaw-opening component of biting attack. As it is known that glutamate excites cell bodies but not axons, the results suggest the specific location of a population of hypothalamic neurones which mediate a major component of biting attack.     

Stimulation of the ventral tegmental area (A10 region) enhances the hypothalamic attack behavior in the cat

The influence of the A10 region of the ventral tegmental area (VTA) on the quiet biting attack evoked by stimulation of the lateral hypothalamic nucleus (LH) was studied. The latency of the biting was considered as reference value and measured with stop-watches; it remained constant when hypothalamic stimulation was performed with the same parameters. Simultaneous activation of the A10 neuron group induced a facilitation of the aggression in the form of a decrease in the biting latency or a display of the attack pattern when LH was stimulated with parameters below the threshold for biting appearance. The facilitatory effect of the A10 neurons of the VTA is discussed.     

Suppression of attack behavior in cats by stimulation of ventral tegmental area and nucleus accumbens

Low frequency (6 pps) stimulation of ventral tegmental area (VTA) and nucleus accumbens (NA) produced EEG synchronization and suppressed attack behavior elicited by hypothalamic stimulation. Both quiet biting and affective attack with rage were suppressed. Autonomic and non-directed somatic motor components of the attack reaction were unaffected.High frequency (60 pps) stimulation of VTA failed to suppress any components of the attack reaction; high frequency stimulation of NA, however, did produce suppression of attack.Low frequency (6 pps) sensory stimulation, delivered by photic or lateral geniculate stimulation, produced EEG synchronization but failed to cause suppression of attack. These results indicate that low frequency stimulation per se does not cause suppression of ongoing behavior.This study demonstrates that VTA and NA, components of the mesolimbic dopamine system, are involved in the inhibition of emotional-type behaviors.     

Afferent projections to affective attack sites in cat hypothalamus

Quiet biting attack by a cat on a rat was elicited by electrical stimulation of sites in the cat's lateral hypothalamus.Horseradish peroxidase was deposited at the attack sites. Cells containing reaction products were found in gyrus proreus, anterior and central medial amygdaloid nuclei, lateral and medial preoptic areas, substantia innominata, the bed nuclei of stria terminalis, and anterior commissure. The dorsomedial area of the hypothalamus, paraventricular nucleus, suprammamillary region, and posterior hypothalamic area also contained reactive cells. In the midbrain the ventral tegmental area of Tsai, the dorsal and superior central nuclei of the raphe, central gray matter and interpeduncular nucleus were regions with reactive cells. In the pontine region, the locus coeruleus, parabrachial nuclei, nucleus of the lateral lemniscus, and the dorsal tegmental nucleus of Gudden all had reactive cells.There are many structures which send afferent projections to quiet attack sites located in the hypothalamus and the pontine tegmentum. The commonality of afferents to attack sites lends credence to the notion that a complex, distributed, interactive network underlies the neural basis of attack behavior.     

Afferent projections related to attack sites in the pontine tegmentum

Attack by a cat on a rat was elicited by electrical stimulation of the ventral parabrachial nucleus or the paralemniscal pontine reticular formation. The attack was quiet and it differed from similar behavior elicited at other sites in that the cat not only bit the rat but struck it with its paw.Horseradish peroxidase was deposited at the attack sites. Cells sending projections to the attack sites were located in gyrus proreus, anterior, central, and medial amygdala, the bed nucleus of the stria terminalis, lateral, dorsal and perifornical hypothalamus, as well as the central gray matter, superior colliculus, midbrain reticular formation, locus coeruleus, nucleus of the lateral lemniscus, and nucleus interpositus. Additional sites of cells of origin appeared with less regularity. This distribution of sites correlates well with the sites from which attack can be elicited or modulated.     

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.     

Heart rate and blood pressure responses to electrical stimulation of the central nervous system in the pigeon (Columba livia)

An extensive stereotaxic stimulation study of the pigeon brain was conducted with monitoring of heart rate, arterial blood pressure and respiration. Rostrally, short latency tachycardia, hypertension and hyperpnea were elicited from the archistriatum, occipitomesencephalic tract and hypothalamus. In addition, blood pressure decreases followed by long latency tachycardia were elicited from the septal complex, although occasionally slight bradycardia occurred. Tachycardia, hypertension and hyperpnea were elicited from many midbrain sites including the lateral reticular formation, ventrolateral tegmentum, ventral area of Tsai, the midline region between nucleus interpeduncularis and the oculomotor complex, and nucleus mesencephalicus lateralis, pars dorsalis. In addition, moderate tachycardia and hypotension were elicited from the central gray and nucleus intercollicularis while tachycardia, hypertension and hyperpnea were elicited from the tegmental area in the region of the occipitomesencephalic tract. At pontine levels, hypertension and cardioacceleration were elicited from a sparsely celled region lateral to the nucleus abducens and from a ventrolateral tegmental region. With respect to respiratory responses, hyperpnea was elicited from the ventrolateral brainstem at all pontine levels and from the dorsomedial region at rostral pontine levels. In caudal pons apnea was the consistent respiratory response to stimulation of the dorsomedial brainstem. In addition, cardio-acceleration, hypertension and apnea were elicited from the region of the deep cerebellar nucleus cerebellus internus and from its major outflow, the uncinate fasciculus. Finally, stimulation in the medulla elicited bradycardia and hypotension from the vagal rootlets, solitary complex, descending vestibular nucleus and lateral aspect of the dorsal motor nucleus just rostral to the obex. Tachycardia and hypertension were elicited from the medial aspect of the dorsal motor nucleus, medullary reticular formation ventral to the vagal rootlets and ventrolateral medulla.     

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 connections of the septal region in the rat

The efferent, afferent and intrinsic connections of the septal region have been analyzed in the rat with the autoradiographic method. The lateral septal nucleus, which can be divided into dorsal, intermediate and ventral parts, receives its major input from the hippocampal formation and projects to the medial septal-diagonal band complex. The ventral part of the nucleus also sends fibers through the medial forebrain bundle to the medial preoptic and anterior hypothalamic areas, to the lateral hypothalamic area and the dorsomedial nucleus, to the mammillary body (including the supramammillary region), and to the ventral tegmental area. The medial septal nucleus/diagonal band complex projects back to the hippocampal formation by way of the dorsal fornix, fimbria, and possibly the cingulum. Both nuclei also project through the medial forebrain bundle to the medial and lateral preoptic areas, to the lateral hypothalamic area, and to the mammillary complex. The medial septal nucleus also sends fibers to the midbrain (the ventral tegmental area and raphe nuclei) and to the parataenial nucleus of the thalamus, while the nucleus of the diagonal band has an additional projection to the anterior limbic area. Ascending inputs to the medial septal nucleus/diagonal band complex arise in several hypothalamic nuclei and in the brainstem aminergic cell groups. The posterior septal nuclei (the septofimbrial and triangular nuclei) receive their major input from the hippocampal formation, and project in a topographically ordered manner upon the habenular nuclei and the interpeduncular nuclear complex. The bed nucleus of the stria terminalis receives its major input from the amygdala (Krettek and Price, '78); but other afferents arise from the ventral subiculum, the ventromedial nucleus, and the brainstem aminergic cell groups. The principal output of the bed nucleus is through the medial forebrain bundle to the substantia innominata, the nucleus accumbens, most parts of the hypothalamus and the preoptic area, the central tegmental fields of the midbrain, the ventral tegmental area, the dorsal and median nuclei of the raphe, and the locus coeruleus. The bed nucleus also projects to the anterior nuclei of the thalamus, the parataenial and paraventricular nuclei, and the medial habenular nucleus, and through the stria terminalis to the medial and central nuclei of the amygdala, and to the amygdalo-hippocampal transition area.     

Electrophysiological studies of the septal nuclei: I. The lateral septal region

Electrophysiological studies of the lateral septal region were performed on acutely prepared cats. The data indicate that the lateral septal region consists of two functionally distinct zones: a dorsal zone (i.e., dorsal septal nucleus) and a ventral zone (i.e., lateral septal nucleus). The dorsal septal nucleus receives a heavy ipsilateral fimbria projection, but receives no projection via the ventral septal afferent system. There is no return projection through the fimbria. Test responses recorded from the dorsal septal nucleus show prolonged periods of suppression. The lateral septal nucleus receives a lesser share of the ipsilateral fimbria input, but does receive input via the ventral septal afferent system. Convergence upon single cells between ipsilateral fimbria and ventral septal afferent input was an outstanding feature of lateral septal nucleus organization. Cells in the lateral septal nucleus project out of the lateral septal region in both dorsal and ventral directions.     

Efferent connections of the hippocampal formation in the rat.

In this investigation the projections of the hippocampal formation to the septal area and hypothalamus were studied in the rat with the combined use of 3H-amino acid radioautography and horseradish peroxidase histochemistry. The results indicate that all of the fibers which project to the hypothalamus and the majority of fibers which project to the septum arise from the subicular cortex and not from hippocampal pyramidal cells. The projection to both of these areas are topographically organized along the longitudinal axis of the hippocampal formation. Specifically, fibers from subicular cortical cells situated at the septal end of the hippocampal formation which project through the medial part of the dorsal fornix terminate in the dorsomedial quadrant of the lateral septal nucleus and in the dorsal portion of the pars posterior of the medial mammillary nucleus. Fibers from progressively more posteroventral levels of the hippocampal formation which project through more lateral portions of the dorsal fornix and fimbria terminate in progressively lateral and ventral quadrants of the lateral septal nucleus and in progressively more ventral portions of the pars posterior. Concerning the specific origin of the fornix system, fibers from only the prosubiculum and subiculum project through both the pre- and postcommissural fornix. Hippocampal pyramidal cells from all CA fields have a restricted projection through the precommissural fornix and terminate in the caudal half of the septum while the presubiculum projects solely through the postcommissural fornix. The medial corticohypothalamic tract (MCHT) was found to arise from cells located in anterior ventral levels of the subicular cortex. Fibers from this tract appeared to be distributed throughout the pericellular region of the entire ventromedial extent of the hypothalamus from the level of the suprachiasmatic nucleus through the level of the medial mammillary nucleus. In this way, the mammillary bodies receive input from the subicular cortex via two routes: the descending column of the fornix and the MCHT.     

Differential control of aggression by the midbrain

Electrical stimulation of the midbrain tegmentum can produce differential modulation of quiet biting attack and affective defense behavior elicited from the hypothalamus of the cat. Stimulation of the lateral half of the tegmentum facilitated quiet biting attack and suppressed affective defense. Conversely, stimulation of the medial tegmentum suppressed quiet biting attack and facilitated affective defense. These results clearly indicate a topographic organization of modulatory sites controlling hypothalamic aggression within the midbrain tegmentum.     

Dopaminergic regulation of quiet biting attack behavior in the cat.

The present study provides evidence for the involvement of dopamine in the regulation of quiet biting attack behavior. Utilizing monopolar electrodes, quiet biting attack was elicited by electrical stimulation of lateral hypothalamus in five cats. After stable baseline response latency values were established, the nonselective dopamine agonist, apomorphine, was administered peripherally (IP, 1.0, 1.4 and 1.8 mg/kg), and its effects upon the attack response were identified. Apomorphine significantly facilitated the occurrence of quiet biting attack in a dose- and time-dependent manner. Conversely, quiet biting attack behavior was also suppressed in a dose- and time-dependent manner by the selective D2 antagonist, spiperone (0.2, 0.4 and 0.8 mg/kg), but not by the selective D1 antagonist, SCH 23390 (0.8 mg/kg). Moreover, pretreatment with spiperone (0.2 mg/kg) completely blocked the facilitatory effects of 1.4 mg/kg of apomorphine, while SCH 23390 (0.8 mg/kg) pretreatment failed to alter apomorphine-induced facilitation of the attack response. In addition, neither apomorphine nor spiperone altered response latencies for hypothalamically elicited circling behavior. The results suggest that dopamine plays a significant role in the regulation of quiet biting attack behavior.