Anterior Limbic Cortex Research Articles

Brain-aging related protein expression and imaging characteristics of mice exposed to chronic hypoxia at high altitude.

To determine changes in protein expression related to brain aging and imaging features in mice after chronic hypoxia exposure at high altitude. A total of 24 healthy 4-week-old mice were randomly divided into high altitude hypoxia (HH) and plain control (PC) groups (n = 8 per group). HH mice were transported from Xi'an (450 m above sea level) to Maduo (4,300 m above sea level) while PC mice were raised in Xi'an. After 6 months, 7.0T magnetic resonance imaging (MRI) was performed. All mice completed T2-weighted imaging (T2WI), diffusion tensor imaging (DTI), resting-state functional MRI (rs-fMRI), arterial spin labeling (ASL), and magnetic resonance angiography (MRA) examinations. Next, brain slices were prepared and Nissl staining was used to observe morphological changes in neurons. Ultrastructural changes in neurons were observed by transmission electron microscopy. Expression changes of Caspase-3, klotho, P16, P21, and P53 at the gene and protein levels were detected by real-time PCR (RT-PCR) and Western blot. The number of neuronal Nissl bodies in the hippocampus and frontal cortex was significantly decreased in the HH group compared to the PC group. Some hippocampal and frontal cortical neurons were apoptotic, the nuclei were wrinkled, chromatin was aggregated, and most mitochondria were mildly swollen (crista lysis, fracture). Compared with the PC group, the HH group showed elevated expression of caspase-3 mRNA, P16 mRNA, P21 mRNA, and P53 mRNA in the hippocampus and frontal cortex. Expression of Klotho mRNA in the frontal cortex was also significantly decreased. Western blot results showed that caspase-3 protein expression in the hippocampus and frontal cortex of the HH group was increased compared with the PC group. Moreover, there was decreased Klotho protein expression and significantly increased P-P53 protein expression. Compared with the PC group, expression of P16 protein in the frontal cortex of the HH group was increased and the gray matter (GM) volume in the left visceral area, left caudate nucleus, and left piriform cortex was decreased. Furthermore, the amplitude of low frequency fluctuation was decreased in the left posterior nongranular insular lobe, right small cell reticular nucleus, left flocculus, left accessory flocculus, and left primary auditory area, but increased in the GM layer of the left superior colliculus. Regional homogeneity was decreased in the left and right olfactory regions, but increased in the left bed nucleus. After exposure to high altitude, functional connectivity (FC) between the bilateral caudate nucleus and thalamus, corpus callosum, cingulate gyrus, anterior limbic cortex, globus pallidus, and hippocampus was weakened. FC between the right caudate nucleus and hypothalamus and entorhinal cortex was also weakened. The fractional anisotropy value of the left hippocampus was decreased in the HH group. Compared with the PC group, the HH group showed significantly increased inner diameters of the bilateral common carotid artery and left internal carotid artery. The cerebral blood flow values of the bilateral cortex and bilateral hippocampus in the HH group did not change significantly. Taken together, our findings show that chronic hypoxia exposure at high altitude may promote neuronal apoptosis and abnormal expression of related proteins, changing the structure and function of brain. These changes may contribute to brain aging.

Cell Reactions in the Limbic Cerebral Cortex After Ethanol Poisoning, Alcohol Abstinence and Chronic Alcohol Intoxication in Humans

The aim of the study was to identify characteristics of the neuron reactions and macroglial cells in the limbic cerebral cortex after ethanol poisoning, alcohol withdrawal and chronic alcohol intoxication in humans. Material and methods. The study included Nissl stained histological sections in the area 24 b in healthy people (n=5), in people died from ethanol poisoning (in the period of ethanol resorption, n=5) and in people during alcohol withdrawal (at the end of ethanol elimination, n=5) having early signs of an alcohol disease. The number and proportion of neurons in identification groups (unmodified/low- modified, hypochromic, shriveled hyperchromic, “shadow cells”), the number of satellite cells and the ratio of satellite cells to the number of unchanged neurons (glio-neuronal index), the average area of the neuron bodies was calculated on horizontal sections of the anterior limbic cortex 1 mm 2 in area. Results. The study proposed to distinguish between acute (or transient), delayed and chronic response of neuronal cells. The acute reaction that develops during ethanol poisoning is expressed by acute swelling of neurons and results from a combination of altering factors: the toxic effects of ethanol and the overproduction of catecholamines. The acute reaction is more pronounced in the dopaminergic layer III of the anterior limbic cortex than in layer V. It is transient, since in the period of alcohol withdrawal (ethanol elimination) it regresses and becomes delayed. The latter is to increase and dominate the proportion of atrophic reduced in the size of lowmodified and atrophic wrinkled neurons, increased phagocytic activity of dead neurons, as well as the development of compensatory-adaptive reaction of the satellite form of glia, the most pronounced in layer III. Delayed reaction of neurons is due to the weakening and cessation of acute effects of toxicants; as a result, the signs of previous long-term intoxication effects of ethanol, its toxic metabolites and increased concentrations of catecholamines, hich caused cell atrophy, come to the fore. Chronic cell response is expressed by a significant increase in the proportion of neurons-"shadows", the number of macroglial cells and atrophic wrinkling of neurons. In people with early manifestations of an alcohol disease, signs of acute neuronal damage are combined with signs of atrophic ones.

Study on functional connectivity between the subgenual anterior cingulate cortes and limbic cortices in predicting the efficacy of early antidepressant treatment outcome

Objective To explore the role of functional connectivity(FC) between the subgenual anterior cingulate cortes(sgACC) and limbic cortices in predicting the efficacy of early antidepressant treatment. Methods Resting state magnetoencephalography(MEG) data were collected from 32 patients with major depressive disorder(MDD) and 20 matched healthy control subjects at baseline.According to whether the HAMD17 total score reduction rate reached 50% after 2 weeks, the patients were divided into responder group and non-responder group.The difference of the FC, the relationship between the FC and the change rate of HAMD17 were explored. Results Compared with controls, MDD patients showed decreased connectivity of the sgACC with the right hippocampus(MNI coordinate: x=30, y=-3, z=-24; F=5.11, P=0.028), the right amygdala(MNI coordinate: x=22, y=-2, z=-15; F=6.90, P=0.012) and the left amygdala(MNI coordinate: x=-24, y=-6, z=-16; F=5.75, P=0.020). Compared with non-responders, the connectivity of the sgACC with the right hippocampus(MNI coordinate: x=30, y=-3, z=-24; F=8.74, P=0.0065), the right amygdala(MNI coordinate: x=22, y=-2, z=-15; F=12.417, P=0.0016) were higher in responders.Pretreatment connectivity of the sgACC with the right hippocampus(r=-0.50, P=0.0066), the right amygdala(r=-0.56, P=0.0018) were negatively correlated with clinical improvement.ROC analyses confirmed the value of the connectivity of sgACC with the right hippocampus(area under curve(AUC)=0.71, P=0.042), the right amygdala(AUC=0.73, P=0.029) in classifying responders versus non-responders in 2 weeks of treatment. Conclusion The decreased FC of the sgACC with the right hippocampus and the right amygdala at baseline is associated with a better improvement, which can potentially serve as a treatment outcome biomarker in early curative effect of depression. Key words: Major depressive disorder; Theta wave; Curative effect; Magnetoencephalography; Functional connectivity

Spatial Organization of Oligodendrocytes and Pyramidal Neurons in the Anterior Limbic Cortex in Health and Schizophrenia: New Potentials for Computerized Morphometry

The spatial organization of oligodendrocytes and pyramidal neurons in the anterior limbic cortex in health and schizophrenia was studied using automated two-dimensional image analysis. Layer III of this area of the cortex in schizophrenia showed a 20% reduction in the minimal distance between oligodendrocytes and their nearest neurons and 10% and 9% reductions, respectively, in the mean maximum distance between neurons and their nearest oligodendrocytes. Thus, this automatic image analysis method allows assessment of the spatial organization of neurons and glial cells in the cerebral cortex not only in health, but also in mental pathology.

Morphofunctional Analysis of the Effects of Total Sleep Deprivation on the CNS in Rats

The aim of the present work was to perform a morphofunctional analysis of the effects of total sleep deprivation of different durations on neuron and synapse ultrastructure in the somnogenic formations (layers III-V of the anterior limbic cortex, field CA1 of the dorsal hippocampus, the pontine reticular formation, the dorsal cervical nucleus, and the locus ceruleus) in rats, with assessment of study investigative, comfort, and sexual behavior, as well as food and water consumption. Reparative changes in neurons and synapses after total sleep deprivation lasting 12-24 h were accompanied by increases in all types of behavioral reactions. Repair processes in neurons and synapses were somewhat weakened after total sleep deprivation lasting 36 h, while dystrophic changes affected greater proportions of neurons and synapses, and the numbers of behavioral reactions decreased.

Regional brain gray matter abnormalities in patients with bipolar II disorder: A comparison study with bipolar I patients and healthy controls

Despite the high prevalence and clinical significance of bipolar II disorder (BD II), the underlying pathophysiology is not well explored in previous studies. The purpose of the current study was to investigate brain gray matter abnormalities in BD II. High resolution magnetic resonance brain images from 23 BD II patients, 23 sex- and age-matched patients with bipolar I disorder (BD I) and 23 healthy controls were acquired and processed according to the optimized voxel-based morphometry protocol. The processed gray matter tissue volumes were compared among the three groups. Both the BD II and BD I group showed gray matter deficits in the ventromedial prefrontal regions, compared to controls. The BD I group had widespread gray matter reductions in the bilateral frontal, temporal, parietal and parahippocampal cortices, compared to controls. However, gray matter reductions in these regions were not found in the BD II group. With a less conservative statistical threshold, the BD II group showed additional gray matter deficits in the anterior limbic cortices. Our data suggest that gray matter deficits in the ventromedial prefrontal and anterior limbic cortices are common in both BD II and BD I. On the other hand, different pattern of gray matter abnormalities between BD II and BD I found in this study supports that two subtypes may have different neurobiological characteristics.

NO-dependent mechanisms of amygdalocortical influence

The brain amygdala complex (AC) participates in awide spectrum of motivational and emotional behav-ioral responses, which are accompanied by changes inthe visceral and endocrine systems [1]. AC projectionsto the anterior limbic cortex are an important pathwayof AC effects on the integrative brain functionsinvolved in visceral regulation [2–4].Numerous neuroanatomical data indicate that ACprojections run from the parvicellular region of the ACbasal nucleus to deeper layers of the prelimbic andinfralimbic cortices [5]. However, the neurophysiolog-ical mechanisms of the amygdalocortical effects medi-ated by this connections remain unclear., To date, theinhibitory and excitatory AC effects on cells of the ante-rior limbic cortex have been described in a few reports[3, 6–8], though nothing is known about the neurotrans-mitters of these processes.At the same time, nitric oxide (NO) is generallyknown to be one of the most important neurotransmit-ters and/or neuromodulators in the central nervous sys-tem [9, 10]. NO is synthesized by some cortical cells[11, 12] and plays an important role in the regulation ofcortical processes; in particular, it modulates the releaseof γ-aminobutyric acid and acetylcholine [10, 13].The nitroergic activity of cortical neurons may bealso involved in the mechanisms underlying the ACeffects on the anterior limbic cortex. Nitroergic activitymodulation may change the level of neuronal excitabil-ity in the prelimbic and infralimbic regions and, hence,the sensitivity of these regions to the regulatory influ-ences of other brain structures, including the ACnucleus.We verified this hypothesis in a series of histochem-ical and neurophysiological experiments performed onWistar male rats weighing 250–360 g; the animals wereanesthetized with urethane (1.5 g/kg body weight;intraperitoneal administration). In response to electricalstimulation of the parvicellular part of the AC basalnucleus, the NO-synthase activity in various regions ofthe anterior limbic cortex was studied histochemically(detection of intracellular nicotinamide dinucleotidephosphate diaphorase (NADP-d). In neurophysiologi-cal experiments, the effects of the same AC nucleusstimulation on the neuronal activity of the anterior lim-bic cortex were studied before and after the administra-tion of 7-nitroindasol, a blocker of the neuronalNO-synthase, into the left lateral brain ventricle. Two groups of animals, each containing four rats(the control one without stimulation and the group ofelectrically stimulated animals) were used in his-tochemical studies. The surgical preparation was thesame in both groups. The parvicellular part of the basalAC nucleus was subjected to a monopolar electricalstimulation in a region with the following coordinates:3.3 mm caudal of bregma, 5.0 mm lateral of the medianline, and about 7.0 mm away from the dorsal brain sur-face; tungsten electrodes in varnish insulation wereused (tip diameter, 50–60 µm; resistance, 80–100 kΩ).Three series of 0.5-ms rectangular pulses were used(current, 30–50 µA). The pulse frequency in a serieswas 50 pulses per second, the series length was 10 s,and the interval between series was 20 s.On completion of the stimulation, the animals weretranscardially perfused with 4% paraformaldehydesolution; 24 h later, 30-µm frontal sections across theanterior limbic cortex were made using a freezingmicrotome. The sections were treated histochemicallyto detect NADP-d according to a modified method ofScherer-Singler et al. [14]. NADP-d-positive neuronswere located, and their number and optical densitywere determined on the cortical sections using animage-analyzing device, which was connected with apersonal computer; the program packages Video TestMaster 4.0 and Image Tool were used. The neuronaloptical density was expressed in arbitrary units(arb. un.) within a range from 0 (a white object) to 1.55(a black object).Neurophysiological experiments were performed on34 rats. In this experimental series, the parvicellularpart of the AC basal nucleus was stimulated by solitaryrectangular pulses with the same parameters. The neu-ronal responses from the anterior limbic cortex were

Kindling antagonism: interactions of the amygdala with the piriform, perirhinal, and insular cortices

We employed the kindling antagonism paradigm to characterize the role of the amygdala (AM), piriform cortex (PIR), perirhinal cortex (PRH), and insular cortex (INS) in the propagation and expression of generalized seizures. Alternating kindling stimulation was delivered to the AM and either the PIR, PRH, or INS. We found that kindling from the AM was retarded by stimulation only of the deep layers of both the INS and anterior PRH. Kindling antagonism was specific to the anterior cortical regions, since neither the posterior PRH or PIR were capable of antagonizing AM kindling. The results strongly implicate the deep layers of anterior limbic cortex in establishment of antagonism of AM kindling.

Limbic cortical influences to the vagal input neurones of the solitary tract nucleus.

In acute experiments on cats, electrical stimulation of the anterior limbic cortex was shown to modulate activity of vagal input neurones of the nucleus of the tractus solitarius. In the majority of the solitary tract nucleus neurones the responses induced by electrical stimulation of the vagus were depressed by the stimulation of anterior limbic cortex. Under these conditions the patterns of responses or their latency were changed. Our results are discussed with respect to possible mechanisms for cortical control of sensory transmission in the nucleus of the tractus solitarius.

Adaptogenic significance of serotonin in dogs emerging from experimental neurosis.

1. The administration of 500 μm serotonin bilaterally over a period of four days into the anterior limbic cerebral cortex prevents development of experimental neurosis in dogs and also prevents the increase in the blood serotonin content usually observed in neurosis. 2. Small 5-hydroxytryptophan doses have a therapeutic effect on neurosis only on the days when the substance is administered. During the subsequent period the neurotic changes in the higher nervous activity are preserved, the blood serotonin content remaining increased. 3. The results of this and the preceding investigation suggest that the intensification of the activity of the serotoninergic system in neurosis is one of the adaptogenic factors facilitating the overcoming of neurosis.

Anterior limbic unit activity during delayed response in cats

The extracellular activity of 328 units was recorded from the anterior limbic cortex of cats performing a spatial delayed response task (DR). The DR task required the cat to make a lever-press response after a delay period of a few seconds to a previously cued location. Of the cells recorded, 139 (42%) showed some relation to DR performance. Task-related units were assigned to one of eight class and type categories consistent with the cell's active phase during the trial periods. Class B units, 23% of the total number of cells recorded, responded during the cue and choice lights. Class C units, 9% of the total recorded, were responsive to the cue and throughout the delay until the lever-press response. Class D units, 4% of the total, were related to the delay phase of DR only. Class E units, 6% of the cells, were active during the cue and displayed activity opposite in sign during the delay. Differential reactivity of units for left and right trials were observed for some units in the B,C, and E response categories, including some cells displaying differential activity during the delay period. It is concluded that visually driven sensory units typically responded to the cue and choice lights, whereas delay related units appeared to represent an intrinsic process, without postural or other external concomitants.

Electrophysiological evidence for a projection from medial prefrontal and anterior limbic cortex toward the medial preoptic area in the cat.

Neurons in cat medial prefrontal cortex, anterior limbic cortex and possibly the indusium griseum were identified by antidromic invasion as having axonal projections towards the medial preoptic region, using both macro- and microstimulation techniques. These projecting axons were found to be of slow conduction velocity (0.2-4.8 m/s) and to in some cases also send branches towards the anteromedial thalamus, mediodorsal thalamus, ventromedial tegmentum, basolateral amygdala or medial forebrain bundle. Threshold-depth curves for axons excited by microstimulation in the medial preoptic region were very steep, with proportionality constants of 0.3-7.1 micron/microA. Calculations based on the threshold-depth curves confirmed that microstimulation was most probably only activating axons within the MPO, and current spread to lateral fibers of passage following macrostimulation in the MPO was not detected in the branching studies.

Glutamate-induced vocalization in the squirrel monkey

In the squirrel monkey, 164 brain sites yielding vocalization when electrically stimulated were tested for their capability to produce vocalization when injected with mono-sodium- l-glutamate. The sites were located in the anterior limbic cortex, n. accumbens, substantia innominata, amygdala, n. striae terminalis, hypothalamus, midline thalamus, field H of Forel, substantia nigra, periventricular and periaqueductal gray, inferior colliculus, reticular formation of midbrain, pons and medulla, inferior olive, lateral reticular nucleus and nucleus of solitary tract. Of the 164 sites tested, 31 were positive. These were located in the substantia innominata, caudal periventricular and periaqueductal gray, lateral pontine and medullary reticular formation. While all the calls obtained from the the forebrain and midbrain had a normal acoustic structure, most pontine and all medullary vocalizations had an artificial character. It is concluded that: (1) the substantia innominata, caudal periventricular and periaqueductal gray, lateral pontine and medullary reticular formation represent relay stations of vocalization-controlling pathways; (2) the periaqueductal gray represents the lowest relay station above the level of motor coordination; (3) neurons responsible for motor coordination of vocalization lie in the reticular formation around the caudal brachium conjunctivum, the superior olive, n. facialis, n. ambiguus and below the n. solitarius; (4) not all areas from which vocalization can be obtained by electrical stimulation of nerve cell bodies, dendrites and nerve endings (in contrast to fibers en passage) also yield vocalization when stimulated with glutamate.

Activity of neurons in limbic cortex during stimulation of somatosensory zones.

The effect of high-frequency and burst stimulation of the first and second somatosensory zones on the activity of identical neurons in the anterior limbic cortex was studied comparatively in acute experiments with cats. A histogramic analysis of neuronal responses in the limbic cortex showed that most background-active cells responded to stimulation of both the first and the second somatosensory zones. Both zones variously adjusted the activity of neurons in the limbic cortex. It was found that the responses in the limbic cortex with the maximum density of the potentials of long-latent reactions are recorded during stimulation of the first somatosensory zone. It was established that the first and second somatosensory zones exert a preferentially activating influence on neurons in the anterior limbic cortex (51.5 and 66.6%, respectively), inhibitory responses comprised 33.3 and 20.0%, while mixed responses were recorded in 15.5 and 13.3% of the neurons, respectively. It was shown that the somatosensory zones exert a modulating influence on the activity of neurons, thus participating in the regulation and processing of information entering the limbic cortex.

Topographical organization of the cortical afferent connections of the prefrontal cortex in the cat

The topographical distribution of the cortical afferent connections of the prefrontal cortex (PFC) in adult cats was studied by using the retrograde axonal transport of horseradish peroxidase technique. Small single injections of the enzyme were made in different locations of the PFC, and the areal location and density of the subsequent neuronal labeling in neocortex and allocortex were evaluated in each case. The comparison of the results obtained in the various cases revealed that four prefrontal sectors (rostral, dorsolateral, ventral, and dorsomedial) can be distinguished, each exhibiting a particular pattern of cortical afferents. All PFC sectors receive projections from the ipsilateral insular (agranular and granular subdivisions) and limbic (infralimbic, prelimbic, anterior limbic, cingular, and retrosplenial areas) cortices. These cortices provide the most abundant cortical projections to the PFC, and their various subdivisions have different preferential targets within the PFC. The premotor cortex and the following neocortical sensory association areas project differentially upon the various ipsilateral PFC sectors: the portion of the somatosensory area SIV in the upper bank of the anterior ectosylvian sulcus, the visual area in the lower bank of the same sulcus, the auditory area AII, the temporal area, the perirhinal cortex, the posterior suprasylvian area, area 20, the posterior ectosylvian area, the suprasylvian fringe, the lateral suprasylvian area (anterolateral and posterolateral subdivisions), area 5, and area 7. The olfactory peduncle, the prepiriform cortex, the cortico-amygdaloid transition area, the entorhinal cortex, the subiculum (ventral, posteroventral, and posterodorsal sectors), the caudomedial band of the hippocampal formation and the postsubiculum are the allocortical sources of afferents to the PFC. The dorsolateral PFC sector is the target of the largest insular, limbic, and neocortical sensory association projections. The dorsomedial and rostral sectors receive notably less abundant cortical afferents than the dorsolateral sector. Those to the dorsomedial sector arise from the same areas that project to the dorsolateral sector and are more abundant to the dorsal part, where the medial frontal eye field cortex is located. The rostral sector receives projections principally from all other PFC sectors, and from the limbic and insular cortices. The projections from the allocortex reach preferentially the ventral PFC sector. Intraprefrontal connections are most abundant within each PFC sector. Commissural interprefrontal connections are largest from the site homotopic to the HRP injection.(ABSTRACT TRUNCATED AT 400 WORDS)

Visually driven units in the anterior limbic cortex of the cat

Single-unit activity was recorded from the anterior limbic cortex of awake cats adapted for chronic recording. Visual stimulation by two stationary spots of white light revealed that 23% of the 170 units recorded from responded with phasic excitation or inhibition to the light onset, light offset, or light onset and offset period of stimulation. These results support the contention that the anterior limbic cortex is a component of the prefrontal cortical network in the cat.

Associational connections between the anterior and postetior cingulate gyrus in rabbit

Reciprocal anatomical connections between anterior and posterior divisions of the cingulate gyrus are described for the rabbit. Cells within the anterior limbic and precentral agranular regions of the rostral cingulate gyrus, predominantly from layer V, send afferebts to layer I of posterior cingulate and retrosplenial cortices. Cells from layers II and III of posterior cingulate and from layer V of retrosplenial cortex project rostrally to the anterior limbic and precentral agranular cortices. These data demonstrate the existence of an associational anatomical system connecting anterior and posterior regions of the cingulate gyrus.

The projections of the ventral tegmental area and adjacent regions: A combined fluorescent retrograde tracer and immunofluorescence study in the rat

The organization of projection neurons in the ventral tegmental area (VTA), and in adjacent parts of the raphe nuclei medial to it (the central and rostral linear, and interfascicular nuclei), the mammillary body (the supramammillary region and the tuberomammillary nucleus), and the substantia nigra have been examined in the rat with Kuypers' retrograde double labeling method, and with a combined retrograde labeling (with true blue)-immunohistochemical method for the demonstration of dopaminergic neurons. First, the distribution, within the VTA and adjacent regions, of dopaminergic and non-dopaminergic cells that project to terminal fields in the telencephalon (nucleus accumbens, lateral septum, pre- and supragenual fields of the anterior limbic cortex, amygdala, dorsal hippocampus, and entorhinal area), in the diencephalon (lateral habenula), and in the brainstem (locus coeruleus, and parabrachial nucleus) was determined. Then, 15 different combinations of injections of the tracers bisbenzimide and true blue into different terminal fields were made to determine whether individual cells in the region of the VTA send collaterals to more than one site. Taken together, the results indicate that essentially separate groups of cells in the VTA and adjacent regions of the raphe project to each terminal field. In addition, each group can be further divided into dopaminergic and non-dopaminergic components, although the proportion of dopaminergic cells in each group can vary from over 80% (e.g., to the nucleus accumbens) to less than 1% (to the lateral habenula and to the locus coeruleus). In addition, it was found that the supramammillary region, which contains a dense extension of the A10 cell group in its medial part, and the tuberomammillary nucleus, project to, or through, most of the regions injected with retrograde tracers. Virtually all of the projections from the VTA and adjacent regions are partially crossed, the percentage of cells on the uninjected side ranging from over 40% (e.g., for locus coeruleus injections) to only about 2% (e.g., for amygdalar injections). Most of the groups of projection neurons in the region of the VTA are considerably intermixed with the exception of those that project to the lateral septum, to the lateral habenula, and to the hippocampal formation, which are concentrated in ventral and medial parts of the VTA, and in the raphe nuclei medial to the VTA. It was concluded that in the ventral part of the midbrain, essentially separate groups of aminergic and non-aminergic neurons in both the reticular formation (VTA) and in the adjacent nuclei of the raphe project bilaterally to a variety of similar terminal fields in the telencephalon, diencephalon, and brainstem. Further work at the single cell level is needed to determine whether these cell groups are differentially innervated by known inputs to the VTA and adjacent regions, most of which appear to descend through the medial forebrain bundle from sites in the limbic system and hypothalamus.

Anatomical and physiological evidence for a relationship between the ‘cingular’ vocalization area and the auditory cortex in the squirrel monkey

With the aid of the autoradiographic tracing technique the projections from cortical limbic vocalization areas to the auditory cortex in the superior temporal gyrus were studied in the squirrel monkey. The vocalization areas were identified by exploring the anterior limbic cortex with moving electrodes until a site was found where electrical stimulation yielded vocalization. Projections from the region around the cingulate sulcus and supracallosal anterior cingulate gyrus have their terminal fields in the lower part of the superior temporal gyrus (STG) and upper bank of the superior temporal sulcus. Injections just in front of the genu of the corpus callosum and in the subcallosal gyrus and gyrus rectus lead to terminal fields in the middle part of STG. No projections were found in the upper part of STG, i.e. the primary auditory cortex. To test the functional properties of this pathway, action potentials of single neurons in the auditory cortex were recorded during electrical stimulation of the cingular vocalization area. From a total of 135 STG neurons, an effect on spontaneous activity was seen in 27 cells. All except one of these neurons also reacted to acoustic stimuli. In most cases, stimulation of the cingular area caused a decrease in the discharge rate of the STG neurons. In 4 neurons, stimulation of the vocalization area had an influence on the acoustic reactivity of the STG neurons. The results provide evidence that during phonation the ‘cingular’ vocalization area exerts a predominantly inhibitory influence on auditory cortex neurons. This effect probably is mediated via the extreme capsule. Its possible function is discussed.

Evidence for selective loss of brain dopamine- and histamine-stimulated adenylate cyclase activities in rabbits with aging

Dopamine-stimulated adenylate cyclase activity in striatum and both dopamine- and histamine-stimulated adenylate cyclase activity in hypothalamus, frontal cortex and anterior limbic cortex declined by about 50% as rabbits aged from 5.5 months to 5.5 years of age. These changes were primarily in maximal response to amine although an additional component involving decreased affinity in the case of dopamine may also be present. In contrast, dopamine-stimulated adenylate cyclase of retina and both basal and guanyl-5'-yl-imidodiphosphate (Gpp(NH)p)-stimulated activity in these regions were not altered with age. There was no measurable decrease in the old animals in either dopamine or norepinephrine concentration in striatum, anterior limbic cortex or retina, or in choline acetylase activity or [3H]quinuclidinylbenzilate binding in striatum, anterior limbic cortex or frontal cortex. It is proposed that selective age-dependent decreases in transmitter receptors coupled to adenylate cyclases occur in the absence of or independent from neuronal cell loss, as evidenced by the retention of the other biochemical markers.