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Brain Development The brain is made up of circuits. Chen and Kriegstein analyzed how one particular circuit functions differently in developing and mature mouse brains (see the Perspective by Spitzer). This circuit connects the brain's diencephalon to the cortex. Early in development, the circuit is excitatory and affects how the cortical neurons it touches build their dendrites and synapses. Later on, after the fundamentals of brain construction are in place, the circuit switches to inhibitory functions, helping the brain resist epileptiform activity. Science , this issue p. [554][1]; see also p. [510][2] [1]: /lookup/doi/10.1126/science.aac6472 [2]: /lookup/doi/10.1126/science.aad4876

Amnesic patients and nondemented patients with Parkinson's disease were given a probabilistic classification task in which they learned which of two outcomes would occur on each trial, given the particular combination of cues that appeared. Amnesic patients exhibited normal learning of the task but had severely impaired declarative memory for the training episode. In contrast, patients with Parkinson's disease failed to learn the probabilistic classification task, despite having intact memory for the training episode. This double dissociation shows that the limbic-diencephalic regions damaged in amnesia and the neostriatum damaged in Parkinson's disease support separate and parallel learning systems. In humans, the neostriatum (caudate nucleus and putamen) is essential for the gradual, incremental learning of associations that is characteristic of habit learning. The neostriatum is important not just for motor behavior and motor learning but also for acquiring nonmotor dispositions and tendencies that depend on new associations.

Retrograde fluorescent tracers were used to demonstrate a previously unknown but sizable direct gamma-aminobutyric acid (GABA)-containing neuronal pathway from the zona incerta to the neocortex in rats. This incertocortical pathway was found to project bilaterally to the entire neocortex and exhibited a rough corticotopic organization. Many of the zona incerta neurons projecting to the parietal and occipital cortices could also be immunohistochemically stained with antibodies to glutamic acid decarboxylase and GABA. Few of these neurons were immunoreactive to tyrosine hydroxylase antibodies, which identify dopamine-containing neurons. Injections in the frontal and entorhinal cortices labeled many neurons near or within the dopaminergic A13 subdivision of the zona incerta. In addition, the incertocortical system was found to be significantly larger during early postnatal (2 to 3 weeks) development. The projection pattern of this newly discovered pathway resembles that of the monoaminergic and cholinergic systems, arising from the brainstem and forebrain, suggesting possible similarities of function.

Hatched chicks with chimeric brains containing cells from both the domestic chicken (Gallus gallus domesticus) and the Japanese quail (Coturnix coturnix japonica) have been produced by transplantation of various regions of the neural tube at the 8- to 15- somite stage. The positions of host and donor cells relative to graft boundaries observed throughout embryonic development and after hatching implicated both radial and tangential cell movements in brain morphogenesis. In addition, transplants containing the entire quail mesencephalon and diencephalon resulted in the transfer of certain aspects of species-typical crowing behavior.

A sexually dimorphic cell group is described in the preoptic area of the human hypothalamus. Morphometric analysis revealed that the volume of this nucleus is 2.5 +/- 0.6 times (mean +/- standard error of the mean) as large in men as in women, and contains 2.2 +/- 0.5 times as many cells. Between the ages of 10 and 93 years, the nucleus decreases greatly in volume and in cell number. Although no function has yet been established for this nucleus, it is located within an area that is essential for gonadotropin release and sexual behavior in other mammals.

Sensory events and the representation of past experience cause distinctive changes in the electrical activity of widespread regions of the brain. These regions have similar roles in the engram in the sense that they all seem to participate in responses to external events and in subsequent representations of these events. However, the relative contribution of these processes to the activity of different brain regions is quantitatively different, in that some regions are much more strongly affected than others. These results may constitute the basis for reconciliation of localizationist and antilocalizationist views of brain function.

Injection of norepinephrine in the lateral ventricles of rats recovering from lateral hypothalamic anorexia caused immediate feeding and, frequently, overeating. Intraventricular administration of the alpha-noradrenergic blocker, phentolamine, suppressed feeding in both normal rats and rats that had recovered from lateral hypothalamic lesions. Feeding is reinforced by ascending medial forebrain bundle fibers that form alpha-noradrenergic synapses in the hypothalamus and forebrain. Damage to these fibers suppresses feeding by reducing noradrenergic transmission and, hence, the rewarding value of food. Recovery of feeding after hypothalamic lesions coincides with the recovery of noradrenergic reward function.

The coronavirus, mouse hepatitis virus strain A59 (MHV-A59), causes mild encephalitis and chronic demyelination. Immunohistochemical techniques showed that MHV-A59-infected C57BL/6 mice contained dense deposits of viral antigen in the subthalamic nucleus and substantia nigra, with fewer signs of infection in other regions of the brain. The animals showed extra- and intracellular vacuolation, neuronal loss, and gliosis in the subthalamic-nigral region. Such localization is unprecedented among known viral encephalitides of humans and other species. This infection by a member of a viral class capable of causing both encephalitis and persistent infection in several species may be related to postencephalitic parkinsonism.

Cells originating from one of the first two blastomeres of the frog embryo were labeled either by injecting them with horseradish peroxidase or by changing the ploidy of one blastomere. Both methods show the labeled cells confined to the same side of the brain as the labeled blastomere except for cells that have moved from the opposite side into the ventral diencephalon and ventral part of the retina. Reciprocal movement of cells from each side of the prospective forebrain into the prospective retina on the opposite side starts before the neural tube closes and results in the formation of an incipient optic chiasma which may provide the pathway for optic axons to grow from the retina to the opposite side of the brain.

Sex steroid hormones and catecholamines have physiological interactions in the brain. By the combined use of autoradiography and fluorescence histochemistry, steroid hormone target sites and catecholamine neurons were visualized simultaneously in the same tissue preparation. By this dual localization method, [3H]estradiol and [3H]dihydrotestosterone target sites were identified in nuclei of many catecholamine cell bodies in the brainstem, and catecholamine nerve terminals were observed near certain steroid hormone target neurons. These results suggest close anatomical interrelations between steroid hormone sites of action and catecholamine sites of production and action in the brain.

The lateral habenula is one of the few forebrain areas that project to the midbrain raphe nuclei. Electrical stimulation of the habenula markedly suppressed serotonergic neurons in the midbrain raphe. The suppression was blocked by systemic or microiontophoretic administration of picrotoxin, which suggests that gamma-aminobutyric acid is the inhibitory transmitter in the habenula-raphe pathway. These results support the concept that the habenula may serve a pivotal role in funneling information from the forebrain to the midbrain raphe.

A monoclonal antibody produced against hippocampal cell membranes labeled the surface of neurons in the rat limbic system. With a few exceptions, all nonlimbic components were unstained. This specific distribution of immunopositive neurons provides strong evidence of molecular specificity among functionally related neurons in the mammalian brain and supports the concept of a limbic system.

A direct hypothalamocerebellar projection in the cat was revealed by means of retrograde transport of wheat germ agglutinin--horseradish peroxidase complex. This appears to be the first demonstration of a significant autonomic input to the cerebellum. The projection has a widespread origin and is bilateral with an ipsilateral preponderance.

The substantia gelatinosa of the mammalian spinal cord is generally believed to be a closed system; that is its neurons are thought to project only to the substantia gelatinosa of the same or the contralateral side. Experiments in monkeys, using injections of the marker enzyme horseradish peroxidase, show that at least some neurons of the substantia gelatinosa project to the thalamus and thus belong to the spinothalamic tract. Such neurons include two cell types intrinsic to the gelatinosa, the central cells and the limitrophe cells of Cajal.

Rats in which ascending dopamine-containing neurons have been unilaterally destroyed by injections of 6-hydroxydopamine are known to rotate after being injected with apomorphine or L-dopa. The rotation is markedly reduced by either (i) ipsilateral electrocoagulations of the caudate-putamen or internal capsule or (ii) ipsilateral coronal knife cuts immediately rostral to the substantia nigra. Neostriatal efferent fibers, in particular the strionigral projection, appear to be required for the expression of this dopamine-dependent behavior.

The subiculum of the primate hippocampal formation stands at the end of a polarized sequence of intrinsic hippocampal efferents and is the source of efferents to the medial frontal cortex, the caudal cingulate gyrus, and the parahippocampal area and amygdala in the temporal lobe. In addition, the subiculum sends subcortical efferents to the septum and diencephalon.

Rats were adrenalectomized 10 days before we estimated in vivo the conversion index of (3)H-tryptophan into radioactive serotonin in brainstem and telediencephalon. We found that the conversion index in the brainstem of adrenalectomized rats is smaller than in the same area of sham-operated rats. Conversely, the conversion index in the telediencephalon was similar in the two groups of rats. The serotonin concentrations were unchanged by adrenalectomy, which suggests that in brainstem the decrease of tryptophan hydroxylase is reflected by the conversion index estimation and not by measurement of serotonin steady-state concentrations.

Patterns of electrical potentials recorded from the brains of sharks exhibit definite relationships to chemical and visual stimuli. Forebrain potentials reflect olfactory processes. Both restrained and free-swimming sharks exhibit mesencephalic responses to light and neural triggering of respiratory reflexes from the medulla. Early evolution of typical vertebrate brain functions, with emphasis upon chemoreception, is indicated

Adrenergic and cholinergic stimulation of several interrelated limbic and diencephalic areas causes the animal to eat and drink, respectively. The brain areas involved may be organized in terms of "Papez circuit" and, more generally, " Nauta circuit" neuroanatomy. However, it is proposed that separate synaptic nets, one for the control of hunger and one for the control of thirst, are deployed throughout the brain at all levels, including neocortical.

Self-stimulation performance of rats was tested with conditioning pulses to the anterior preoptic area of the medial forebrain bundle followed at various intervals by test pulses to the contralateral posterior hypothalamic area of this bundle. Alternatively, conditioning pulses were delivered through the posterior electrode and test pulses were sent through the anterior electrode. The animals' performance in these two test sequences was indicative of (i) synaptic facilitation and (ii) a posterior convergence site of "self-stimulation impulses" in the medial forebrain bundle.

Optic nerve section or destruction of the lateral geniculate nucleus increased the amplitude and elevated the recovery cycle of the cortical response to lateral geniculate radiation stimulation in cats. The lesions may have acted by eliminating tonic inhibitory or occlusive volleys originating in the retina, or both.