Anabolic steroids alter the physiological activity of aggression circuits in the lateral anterior hypothalamus.

Syrian hamsters exposed to anabolic/androgenic steroids (AAS) during adolescence consistently show increased aggressive behavior across studies. Although the behavioral and anatomical profiles of AAS-induced alterations have been well characterized, there is a lack of data describing physiological changes that accompany these alterations. For instance, behavioral pharmacology and neuroanatomical studies show that AAS-induced changes in the vasopressin (AVP) neural system within the latero-anterior hypothalamus (LAH) interact with the serotonin (5HT) and dopamine (DA) systems to modulate aggression. To characterize the electrophysiological profile of the AAS aggression circuit, we recorded LAH neurons in adolescent male hamsters in vivo and microiontophoretically applied agonists and antagonists of aggressive behavior. The interspike interval (ISI) of neurons from AAS-treated animals correlated positively with aggressive behaviors, and adolescent AAS exposure altered parameters of activity in regular firing neurons while also changing the proportion of neuron types (i.e., bursting, regular, irregular). AAS-treated animals had more responsive neurons that were excited by AVP application, while cells from control animals showed the opposite effect and were predominantly inhibited by AVP. Both DA D2 antagonists and 5HT increased the firing frequency of AVP-responsive cells from AAS animals and dual application of AVP and D2 antagonists doubled the excitatory effect of AVP or D2 antagonist administration alone. These data suggest that multiple DA circuits in the LAH modulate AAS-induced aggressive responding. More broadly, these data show that multiple neurochemical interactions at the neurophysiological level are altered by adolescent AAS exposure.

Cross-modal plasticity after monocular enucleation of the adult rabbit.

The mature brain undergoes compensatory reorganization of the primary visual cortex (V1) in response to retinal lesions. This study demonstrates that V1 also supports cross-modal reorganization by observing an increase in tactile responses in V1 after monocular enucleation of the adult rabbit. The proportion of tactile-responsive V1 neurons increased from 0% to 31%, in an area of cortex equivalent to 40 degrees of visual space. Retrograde fiber-tracing analysis suggests that intracortical connections from association areas may underlie these novel responses. Cortical plasticity of this kind may be involved in recovery from sensory system damage and could provide an enhanced sense of touch to the blind.

Electrophysiological and behavioral output of the rat basal ganglia after intrastriatal infusion of d-amphetamine: lack of support for the basal ganglia model.

Dopamine, by acting upon D1 and D2 dopamine receptors located on striatonigral and striatopallidal neurons, respectively, has been postulated to inhibit output from the substantia nigra pars reticulata (SNpr) and internal pallidal segment (GPi). The inhibition of the SNpr/GPi should, in turn, disinhibit the thalamus to facilitate movement. The present study tests this prediction in intact (unlesioned) rats by attempting to correlate changes in the single unit activities of SNpr neurons with motor (i.e. behavioral) responses in the 20-30 min after infusions of d-amphetamine into the striatum. Unilateral injections of amphetamine (20 microg/microl) into either the dorsal-rostral, central, or ventral-lateral striatum failed to appreciably alter behavior and, in parallel electrophysiological studies, failed to consistently or significantly alter the activities of SNpr neurons in either chloral hydrate-anesthetized rats or awake locally anesthetized rats. However, when amphetamine was infused bilaterally into the ventral-lateral striatum (VLS; 20 microg/microl per side), a robust behavioral activation ensued (increased locomotor activity, oral movements, and sniffing) with an onset ranging from immediate to 20 min post-infusion and persisting for at least 40 min. In parallel studies, bilateral amphetamine infusions into VLS also caused changes in the firing frequency of a majority of SNpr neurons. However, the changes in firing were extremely variable and, contrary to expectation, the net population response of SNpr neurons was an increase in firing which corresponded in time with the period of peak behavioral activation. These results show that (i) bilateral but not unilateral activation of striatal dopamine receptors is needed to elicit behavioral and electrophysiological output from the basal ganglia, and (ii) motor activation is apparently not signaled by a generalized inhibition of SNpr firing, as is predicted by the basal ganglia model.

Nociceptive neurons in area 24 of rabbit cingulate cortex.

1. Single-unit responses in area 24 of cingulate cortex were examined in halothane-anesthetized rabbits during stimulation of the skin with transcutaneous electrical (TCES, 3-10 mA), mechanical (smooth or serrated forceps to the dorsal body surface or graded pressures of 100-1,500 g to the stabilized ear) and thermal (> 25 degrees C) stimulation. 2. Of 542 units tested in cingulate cortex, 150 responded to noxious TCES (> or = 6 mA), 93 of 221 units tested responded to noxious mechanical (serrated forceps) and 9 of 47 units tested responded to noxious heat (> 43 degrees C) stimuli. Twenty-five percent of the units that responded to noxious mechanical stimuli also responded to noxious heat stimuli. The only innocuous stimulus that evoked activity in cingulate cortex was a "tap" to the skin and this was effective for 11 of 14 tested units. 3. In 74 units that produced excitatory responses to TCES of the contralateral ear, response latency was 166 +/- 11.3 (SE) ms and response duration was 519 +/- 52.1 ms. 4. Twenty of the 150 units that responded to noxious TCES were initially inhibited. These responses were usually < 1 s in duration (17 of 20 units), whereas responses in the other 3 lasted for over 20 s. 5. Most units had broad receptive fields, because noxious mechanical stimuli anywhere on the dorsal surface of the rabbits, including the face and ears, evoked responses. A small number of units for which the entire body surface was tested (3 of 15 units) had receptive fields limited to the ears, rostral back, and forepaws. 6. Fifteen of 33 units tested had no preferential responses to noxious TCES of the ipsilateral and contralateral ears. Of the remaining units, 10 had a greater response to contralateral and 8 had a greater response to ipsilateral stimuli. 7. The locations of 186 units were histologically verified. Most nociceptive cingulate units were in dorsal area 24b in layers III (n = 35), II (n = 13), or V (n = 9). 8. Cortical knifecut lesions were made in five rabbits to determine if the responses in area 24 were dependent on lateral or posterior cortical inputs. These lesions did not alter the percentage of units driven by noxious stimuli nor response latency. 9. Injections of lidocaine were made into medial parts of the thalamus in six animals and injection and recording sites analyzed histologically.(ABSTRACT TRUNCATED AT 400 WORDS)

Limbic thalamus in rabbit: architecture, projections to cingulate cortex and distribution of muscarinic acetylcholine, GABAA, and opioid receptors.

Nuclei of the thalamus that project to cingulate cortex have been implicated in responses to noxious stimuli, cholinergic and motor functions. The rabbit limbic thalamus may play an important role in these functions, but has not been studied extensively in terms of its cytoarchitecture, the topographical organization of its cortical projections, and differential transmitter regulation of its subnuclei. Therefore, the architecture, projections to cingulate cortex, and radioligand binding were investigated in the anterior, ventral, lateral, and midline nuclei of rabbit thalamus. The anterior nuclei are highly differentiated because both the dorsal and ventral nuclei have parvicellular and magnocellular divisions. Fluorescent dyes were injected into cingulate cortex to evaluate limbic thalamocortical connections. The anterior medial, submedial, and parafascicular nuclei project primarily to anterior cingulate cortex, while they have small or no projections to posterior areas. The ventral anterior and ventral lateral nuclei have a significant projection to dorsal cingulate cortex, including areas 24b and 29d. Projections of the anterior ventral nucleus are topographically organized, since medial parts of the parvicellular division project to rostral area 29, and lateral parts project to caudal area 29. The lateral nuclei and the parvicellular and magnocellular divisions of the anterior dorsal nucleus project with progressively higher densities in the rostrocaudal plane of area 29. Finally, the magnocellular division of the anterior ventral nucleus projects almost exclusively to caudal and ventral area 29, i.e., granular retrosplenial cortex. Ligand binding studies employed coverslip autoradiography and single grain counting techniques. Muscarinic receptor binding was moderate for both pirenzepine and oxotremorine-M in the parvicellular anterior ventral nucleus, while in other nuclei, there was an inverse relationship in the binding for these ligands. Most notably, the anterior dorsal nucleus, which receives no cholinergic input, had very high oxotremorine-M and low pirenzepine binding, while the anterior medial nucleus, which receives a moderate cholinergic input, had the highest pirenzepine binding and very low oxotremorine-M binding. Muscimol binding to GABAA receptors was highest in the anterior ventral nucleus, while it was at moderate levels in the anterior dorsal and lateral nuclei. The binding of Tyr-D-Ala-Gly-MePhe-Gly-ol to mu opioid receptors and 2-D-penicillamine-5-D-penicillamine-enkephalin to delta opioid receptors were both high in the parvicellular and low in the magnocellular divisions of the anterior dorsal nucleus. The magnocellular division of the anterior ventral, the lateral dorsal, and the parafascicular nuclei had high mu opioid binding, while the lateral dorsal and lateral magnocellular nuclei had low levels of delta opioid binding.(ABSTRACT TRUNCATED AT 400 WORDS)

Lateral magnocellular thalamic nucleus in rabbits: architecture and projections to cingulate cortex.

The lateral magnocellular nucleus (LM) contains the largest neurons in the rabbit thalamus, yet its cortical connections have not been described. This study evaluates the architecture, cingulate cortical connections, and spontaneous rate of neuronal discharges in LM. At its maximal mediolateral extent in coronal sections, LM underlies the laterodorsal and lateroposterior nuclei. It has a short medial and long lateral limb, both of which have high levels of cytochrome oxidase activity. On the basis of horseradish peroxidase and fluorescent dye injections, LM projects primarily to area 29 and posterior area 24. Projections to area 29d are topographically organized so that the medial limb of LM projects to rostral area 29d, mid levels of LM where the limbs join project to midlevels of area 29d and lateral parts of the lateral limb project to posterior area 29d. It is mainly the midportion of the lateral and medial limbs that projects to areas 29b and 29c. The anterior parts of these areas receive input from dorsal parts of LM, whereas posterior levels of these areas receive input from ventral LM. The midregion of LM also projects to caudal area 24. Injections of 3H-amino acids into area 29d anterogradely label neuronal processes in LM. Finally, single unit electrophysiological recordings from LM in halothane-anesthetized rabbits showed a unique pattern of spontaneous discharges. Over 70% of the LM neurons cycled through a number of different phases with a mean +/- S.E.M. peak discharge rate of 31 +/- 4.7 Hz. This high rate contrasts with the 17.6 +/- 3.2 Hz rate for neurons that maintained a constant rate of discharge and the 7.5 +/- 1.3 Hz rate of discharges for neurons in nuclei dorsal and ventral to LM. LM neurons are large, have high levels of cytochrome oxidase and spontaneous activity, and project extensively to the posterior cingulate cortex. These features suggest that LM neurons are highly active metabolically and may be fast conducting efferents to cingulate cortex.

Neuronal responses in rabbit cingulate cortex linked to quick-phase eye movements during nystagmus.

1. Responses of single units in area 29 of cingulate cortex were examined in alert rabbits during vestibular and optokinetic nystagmus. Eye movements were measured by optically detecting the position of an infrared light-emitting diode attached to the cornea. 2. Fourteen percent of cingulate cells (68 of 477 isolated units) had responses that were correlated to the occurrence of quick phases. Latencies ranged from 60 ms before to 220 ms after the onset of the quick phase with a mean of 70 ms and standard deviation of 58 ms. Most units responded during or following quick phases, although four units had responses that preceded the quick-phase onset. 3. Unitary responses during quick phases were not due to visual field movement, since these responses occurred in the dark as well as the light. The responses were not dependent upon vestibular stimulation, since responses related to spontaneous saccadelike eye movements were observed in cingulate quick-phase neurons. 4. The majority (37 of 52) of the quick-phase neurons had a directional preference. Approximately equal numbers of directional units responded to quick phases directed ipsilaterally and contralaterally with respect to the recording site. 5. About one-fourth of the quick-phase units were bidirectional (15 of 52) with virtually equal responses to ipsilaterally and contralaterally directed quick phases. 6. Auditory and/or somatosensory responses were observed in only five of the quick-phase cells. All such multimodal units were bidirectional. 7. The quick-phase units were histologically confirmed to be primarily in area 29d of cingulate cortex. Although most cells were located in layer V, some were isolated in layer II-III. 8. Cingulate cortex has reciprocal connections with visual cortex and oculomotor-related thalamic nuclei and projects to the layers of the superior colliculus that are involved in oculomotor control. Responses to quick phases in cingulate neurons may synchronize cingulate cortex responsiveness with the arrival of new, and potentially significant, visual information.

Afferent connections of anterior thalamus in rats: sources and association with muscarinic acetylcholine receptors.

Afferent connections of the anterior thalamic nuclei (ATN) are classically thought to originate in the mammillary body and limbic cortex. This study explores nonlimbic sources of ATN afferents by using retrograde transport of horseradish peroxidase (HRP) to ascertain the relative contribution of these connections. Spread of HRP into adjacent regions was prevented either by removing the overlying cortex or by injecting through permanently implanted cannulas. The main sources of nonlimbic ATN afferents are the pretectum and central gray. Pretectal neurons were HRP-labeled primarily in the contralateral medial pretectal nucleus with a smaller number in the ipsilateral posterior pretectal nucleus. In the central gray, labeled cells were concentrated ipsilaterally in the laterodorsal tegmental nucleus. Additional projections to ATN originate in the reticular and ventral lateral geniculate nuclei of the thalamus, raphe nuclei, peripontine tegmental nucleus, and locus coeruleus. The association of ATN afferents with muscarinic receptors was also explored by means of in vitro receptor autoradiography with the muscarinic ligands propylbenzilylcholine mustard (PrBCM) and pirenzepine (PZ) in normal rats and rats with ablations. Ibotenic acid injections into ATN were used to destroy intrinsic neurons while leaving afferent fibers intact. Whereas such ablations produced statistically significant decreases in PrBCM binding in the anterior dorsal (AD, -45%) and anterior ventral, magnocellular part (AVm, -51%) nuclei, binding in the anterior ventral, parvicellular part (AVp) and anterior medial (AM) nuclei was not significantly decreased. Furthermore, PZ binding in normal rat ATN was significantly less (-72%) than PrBCM binding. These results suggest that a major proportion of muscarinic binding is associated with presynaptic elements. Ibotenic acid ablations of the mammillary body reduced PrBCM binding in ATN whereas lesions in cingulate cortex and laterodorsal tegmental nucleus had no effect. Compared to sham lesion controls, mammillary body lesions resulted in statistically significant decreases in binding bilaterally in AD (-15%), AVm (-19%), and AM (-20%). In conclusion, ATN receive afferents from several nonlimbic regions. Of these inputs, the pretectum may be the primary route through which sensory information reaches ATN. In addition, cholinergic input may modulate activity in projections from the mammillary body to ATN through presynaptic muscarinic receptors.

Rabbit cingulate cortex: cytoarchitecture, physiological border with visual cortex, and afferent cortical connections of visual, motor, postsubicular, and intracingulate origin.

The connections of cingulate cortex with visual, motor, and parahippocampal cortices in the rabbit brain are evaluated by using a modified Brodmann cytoarchitectural scheme, electrophysiological mapping techniques, and the pathway tracers horseradish peroxidase (HRP) and tritiated amino acids. Rabbit cingulate cortex can be divided into areas 25, 24, and 29. Area 29 is of particular interest because area 29d has a lateral extension with a granular layer IV, area 29b has a caudal extension in which the connections differ from anterior area 29b, and there is a prominent area 29e. Cytoarchitectural delineation of the lateral border of area 29d with area 17 closely approximates the medial edge of the visual field representation in area 17 as determined electrophysiologically. The main interconnections between visual and cingulate cortices occur between cingulate areas 24b and 29d and visual areas 18 and medial parts of area 17. Projections between areas 29d and 18 are organized in a loose topographic fashion with rostral parts of each and caudal parts of each being reciprocally connected. Neurons mainly in superficial layer II-III of areas 17 and 18 project to layer I of area 29d, while the reciprocal projection originates from neurons in layer V of area 29d and project mainly to layer I of areas 17 and 18. The medial portion of motor area 8 projects to areas 18 and 29d and has a smaller projection to area 17. Postsubicular area 48 is reciprocally connected with area 29d, and it also projects to areas 29b and c. The subiculum projects to areas 29a and 29c but only to the anterior two-thirds of area 29b not the posterior one-third. Rostral area 29d receives the most extensive intrinsic cingulate projections including those from all major cytoarchitectural divisions. Interconnections between areas 29d and 29b appear to be topographically organized in the rostrocaudal plane. Area 29c projects more heavily to area 29b than vice versa. Finally area 29d projects mainly to area 24b in anterior cingulate cortex. In conclusion, rostral area 29d has extensive connections with visual areas 17 and 18, motor area 8, and all subdivisions of cingulate cortex. In light of these connections, it may play a pivotal role in associative functions of the rabbit cerebral cortex including visuomotor integration.

Characterization of fimbria input to nucleus accumbens.

The hippocampal input to the nucleus accumbens was studied by correlative electrophysiological and anatomical techniques in acutely prepared rabbits. Field and extracellular unitary potentials were recorded in the nucleus accumbens following ipsilateral fimbria stimulation. Analysis of the components of the field response was based on the relevant correlations with extracellular unitary activity. The cellular types that are the recipients of the hippocampal projection were determined by combined intracellular horseradish peroxidase (HRP) and Golgi analyses. The distribution of the hippocampal input was determined by combined field potential and current source density analyses. It was found that the ipsilateral fimbria projection was distributed to the dorsal two-thirds of the nucleus, with the projection being heaviest in the more caudal portions of the nucleus. The negative (N) component of the field response was studied by correlating its behavior with the appropriate extracellular unitary recordings. It was concluded that the N-component represented an envelope of monosynaptically activated action potentials. The positive (P) component of the field response throughout the nucleus accumbens was studied pharmacologically with the iontophoretic administration of bicuculline. The P-components, in both the dorsal and ventral regions of the nucleus, were diminished by bicuculline application, indicating that this potential results from the activation of gamma-aminobutyric acid (GABA) mechanisms. The cell populations that are the targets for the hippocampal projections were studied by the technique of intracellular staining with HRP. These results were correlated with the findings of a Golgi analysis. Two distinct cell types were found to respond in a monosynaptic manner to ipsilateral fimbria stimulation. The most common of the two were the small-to medium-sized spiny neurons, and they were distributed throughout the nucleus. These cells have a spherical dendritic arrangement. The second, and most distinctive, of the cell types were the large aspiny neurons. These cells were distributed medially and caudally in the nucleus. Two of the outstanding features of these cells were the expanse of their dendritic domains and the fact that axons originated from relatively remote portions of the dendrites.

Dopamine action in the nucleus accumbens.

The action of dopamine was studied in the nucleus accumbens of acutely prepared rabbits. Dopamine was applied iontophoretically to those cells and cell populations that responded in a monosynaptic excitatory manner to ipsilateral fimbrial stimulation. This strategy was adopted to isolate the effects of dopamine on postsynaptic receptors thus avoiding the bias resulting from activation of presynaptic dopamine receptors on dopaminergic afferents. Dopamine was found to have a suppressive effect on the excitatory (N) component of the field response and on driven extracellular unitary discharges. The specificity of dopamine's effect with receptors was indicated by the facts that fluphenazine effectively antagonized dopamine's effect, whereas bicuculline did not. The effect of dopamine was dependent on the rate of fimbrial stimulation. Dopamine has a marked suppressive effect on the fimbria-induced response at 0.5 Hz of stimulation but not at 6.0 Hz. This frequency specificity could not be linked directly to a cyclic adenosine 3',5'-cyclic monophosphate (cyclic AMP) mechanism because the iontophoresis cyclic AMP and dibutyryl cyclic AMP had suppressive effects at both 0.5 and 6.0 Hz rates of stimulation. It is suggested that dopamine acts in the nucleus accumbens to increase the "signal-to-noise" ratio. This might be a form of "contrast enhancement" of an incoming hippocampal message.

Cholinergic modulation of mediodorsal thalamic input into cingulate cortex.

Field potentials in cingulate cortex (area 24) produced by electrical stimulation of the mediodorsal thalamic nucleus were diminished by iontophoretic ejection of the cholinergic agonist, carbachol. The effect was frequency dependent: field potentials produced by 7.0 Hz stimulation were reduced by 34%. Potentials produced by 0.5 Hz stimulation were not significantly changed. This reduction was blocked by muscarinic but not nicotinic antagonists.

Cingulate cortex response to electrical stimulation of the mediodorsal thalamic nucleus.

Electrical stimulation of the lateral, parvocellular part of the mediodorsal thalamic nucleus of the rabbit was found to evoke field potentials and drive single cells in the anterior cingulate cortex. Furthermore, the laminar distribution of the field responses and the population of effected cells were dependent on the frequency of the stimulation. Excitatory current sinks were produced in layers I and III (primary layers of mediodorsal input) only when the stimulus frequency was in the theta range (6 to 8 Hz); the majority of cells were reliably driven only by stimulation within this range. Lower-frequency stimulation, e.g., 0.5 Hz, produced a current sink in layer V. Cells that were driven at low frequencies might be antidromically activated. The study suggests that modulation of mediodorsal outflow in the theta range may be necessary for effective information transfer to the cortex.

Effects of CCK-8 in the nucleus accumbens.

The electrophysiological effects of CCK-8 were studied in the rabbit nucleus accumbens. CCK-8 was found to influence neurotransmitter (modulator) systems so as to enhance their action. For example, CCK-8 enhanced the effects of stimulation of the glutaminergic pathways, the fimbria. In addition, when CCK-8 was co-administered with dopamine and acetylcholine, their suppressive effect on the fimbria evoked response was enhanced. Therefore, CCK-8 appears to be capable of enhancing the influence of multiple neurotransmitter (modulator) systems.

Evidence for cholinergic muscarinic receptors on mediodorsal thalamic projections to the anterior cingulate cortex.

Cholinergic muscarinic receptor binding was analyzed in the rat brain anterior cingulate cortex following lesions of the mediodorsal or anterior thalamic nuclei, or the diagonal band of Broca. A significant change in receptor binding was noted only after lesions of the mediodorsal projection, suggesting that cholinergic muscarinic receptors are located on these terminals. These findings suggest that the projection from the diagonal band of Broca which is cholinergic may act as a modulator of the mediodorsal thalamic projection.

Origin of cingulate cortex cholinergic innervation in the rat.

The relative contribution of the n. diagonal band and thalamic nuclei to the cholinergic innervation of the cingulate cortex was examined. Lesions were placed in the n. diagonal band, anterior thalamus, and medial thalamus of rats, and changes in choline acetyltransferase in discrete regions of the cingulate cortex were determined. The n. diagonal band lesion produced a large decrease in choline acetyltransferase activity while the thalamic lesions produced no significant change in activity.

Regional distribution of catecholamines in nucleus accumbens of the rabbit.

The nucleus accumbens is an important telencephalic region, which is the target limbic and mesolimbic pathways. Because of an ongoing physiological study of the effects of dopamine, we wanted to determine regional differences of dopamine and norepinephrine concentrations in the nucleus. As determined by radioenzymatic assays, dopamine levels were not significantly different in the anterior-posterior dimension, averaging approximately 187 ng dopamine/mg protein. Substantial amounts of norepinephrine were found throughout the nucleus, but the levels were significantly higher in the caudal portions of the nucleus, being approximately 4.5 times higher than in the anterior portions.

Histamine: correlative studies in nucleus accumbens.

The role of histamine as a neurotransmitter has been the subject of considerable controversy. Recent evidence suggests it to be involved in such complex activities as arousal and affect. The purpose of the present study is to examine the possible source, function, and pharmacology of histamine in the nucleus accumbens, an area of the brain also implicated in complex activities such as affect. The anatomical studies suggest that the most probable source of the histamine in nucleus accumbens is the complex region lateral to the mammillary nuclei. These areas are the intercalated nucleus and the tuberomammillary nucleus (nuclei gemini hypothalami). To a lesser degree, the supramammillary complex may also contribute histamine-containing axons to the accumbens area. Adenylate cyclase in the rabbit nucleus accumbens displayed activation in response to histamine agonists (histamine, 2-Me-histamine, and 4-Me-histamine). The action of the H1 antagonist promethazine was greater than the H2 antagonist metiamide in reducing enzyme activation by histamine and 2-Me-histamine. In contrast, metiamide was more potent than promethazine toward antagonism of the action of 4-Me-histamine. However, no additive effects were noted when agonists were added in combination. Based upon these data, it is suggested that activation of adenylate cyclase in the rabbit nucleus accumbens is mediated in part by mixed H1 and H2 receptors or cellular disruption reflects the loss of receptor specificity. Physiological studies demonstrated that the H2 agonist 4-Me-histamine had an inhibitory effect on the activity of neurons driven by stimulation of the fimbria. The magnitude of the effect was frequency dependent. The H1 agonist 2-Me-histamine had no significant effect. Iontophoretic application of 4-Me-histamine had minimal effect upon low frequency volleys (0.5 Hz) but had a pronounced effect upon higher frequency volleys (6.0 Hz). These effects were antagonized by metiamide. Iontophoretic application of metiamide alone produced an effect only upon the P component of the field response, which is also bicuculline sensitive. Bicuculline coadministration was also effective in antagonizing the 4-Me-histamine effect. The physiological data suggest that histamine works through H2 receptors in nucleus accumbens, perhaps by potentiating the effects of gamma-aminobutyric acid (GABA). Thus, histamine in nucleus accumbens appears to function as a modulatory substance whose effect is dependent upon the activity of other transmitter and afferent systems.

The relative numbers of oligodendroglia in different brain regions of normal and postnatally undernourished rats.

The relative numbers of oligodendroglia were compared in representative brain regions of 21 day old undernourished and control rats. As a result of postnatal undernutrition which produced half normal body weights and a 10-15 percent reduction in brain weight, the relative numbers of oligodendroglia were slightly increased in photomicrographs of corticospinal tract (a motor tract), medial lemniscus (a sensory tract), red nucleus (a motor nucleus) and somatosensory cortex. Relative numbers were reduced in the corpus callosum, and the thickness of the corpus callosum was significantly reduced. Cell sizes of oligodendroglia were essentially normal throughout the brain, although some reductions of 5 to 6 percent were observed. Areas of brain structures in cross section were essentially unchanged. We have previously hypothesized that nutritionally induced brain hypomyelination results from a reduction in the specific numbers of oligodendroglia and consequently a lasting reduction in the brain myelin concentration. The present results are inconsistent with this hypothesis, as both the density of oligodendroglia and sizes of brain regions are essentially normal. We know from prior work using the same model of nutritional deprivation that myelin synthesis is greatly reduced. Consequently an important depressant effect of undernourishment on oligodendroglia in the developing brain involves either the communication between axons and oligodendroglia leading to myelin induction or the synthetic capacity to make myelin.