150 aphasiacs and 59 controls were examined with a scorable, comprehensive battery, designed to be used by the clinician and the research worker. The subtests of Fluency, Information, Comprehension, Repetition and Naming were added and compared to a hypothetical normal of 100 obtaining the “aphasia Quotient.” This is a measurement of the severity of language impairment. On the basis of their performance on the subtests, the patients were classified according to taxonomic principles into Global, Motor (Broca’s), Isolation, Sensory (Wernicke’s), Transcortical Motor, Transcortical Sensory, Conduction and Anomic groups (in order of severity). This classification is considered a clinically valid baseline for research, diagnosis and prognosis.

A neural net model with random interconnections is shown capable of exhibiting the features of Parkinson’s disease, including cogwheel rigidity, resting tremor, and dysdiadochokinesis. These properties are simulated uniquely for extrapyramidal disease, with spasticity and hypereflexia predicted for other upper motoneuron lesions.

The history of the hypothalamus and neuroendocrinology is so intimately related to the development of our ideas on the disease known as diabetes insipidus, that any discussion of the one must include a discussion of the other. Many authors have compared the history of diabetes insipidus to a comedy of errors. Indeed, the whole problem seems to have fared rather badly from the very beginning when Magnus and Schafer (1901), and Schafer and Herring (1905) demonstrated that extracts of the posterior lobe of the pituitary body had a diuretic effect rather than the antidiuretic effect as we know it today. Furthermore, from a histological point of view, Herring (1908) and later Cushing (1933) were of the opinion that the cellular constituents of the posterior lobe were incapable of secreting the active factors attributed to that lobe and that consequently a search had to be made elsewhere for the secretory cells. Herring (1913) visualized the secreting cells as coming from the pars intermedia and migrating into the pars nervosa where they degenerated and released the “hormones”. Cushing (1933) fully subscribed to this and in 1933 stated rather emphatically that “it is scarcely conceivable that the neural core of the lobe is capable independently of elaborating a hormone.”

The results of lesion, stimulation, deafferentation, implantatión and transplantation studies employed in the identification of hypophysiotrophic control areas in the hypothalamus to date suggest the following probable locations: corticotropic releasing factor (CRF) is formed in a diffuse area along the base of the median eminence, if not the base of the entire hypothalamus. Follicle stimulating hormone releasing factor (FSHRF) is elaborated in the paraventricular-suprachiasmatic areas but its cyclic control may reside in the anterior hypothalamic area. Luteinizing hormone (LH) is controlled by luteinizing hormone releasing factor (LHRF) formed in the suprachiasmatic area: its cyclic control may be in the preoptic area. Prolactin is controlled by prolactin inhibiting factor (PIF) localized in a diffuse area comprising the ventromedial, dorsomedial, arcuate and paraventricular nuclei. The hypothalamic area involved in thyroid control is also rather large, since thyrotropin stimulating hormone releasing factor (TSHRF) has been found in an area including the supraoptic and chiasmatic nuclei. Growth hormone releasing factor (GHRF) is elaborated in a rather narrow zone, the ventromedial hypothalamic nuclei.

Our light, and electron microscopic (EM) findings within the hypothalamic supraoptic (SO) and paraventricular (PV) nuclei of the normal female rabbit are in agreement with those reported earlier by other investigators for the same nuclei of the dog and rat. The neurons of these nuclei are the hypothalamic synthesis sites of the neurohypophyseal hormones.

With the exception of the arcuate nucleus, none of the hypothalamic nuclei associated with the control of adenohypohpyseal function have been studied extensively with the electron microscope. On the basis of our EM findings within the female rabbit hypothalamus, all neurons observed within the preoptic (PO) and suprachiasmatic (SCH) nuclei of the non-mated control animal were morphologically identical to the conventional neuron as described by Peters, Palay and Webster (1970). However, following coitus, castration and laparotomy, many neurons of these nuclei showed subcellular changes that have been repeatedly associated with enhanced protein synthesis. These large ‘neurosecretory’ neurons were usually located near capillaries and characterized by their well developed Rough endoplasmic reticulum (RER) and Golgi profiles, dense populations of mitochondria and lysosomes and by the presence of a homogeneous population of densecore vesicles (DCV) showing a peak distribution of 120-140 nm. Since similar neurons were not observed within the PO and SCH of the normal control rabbit it is suggested that we were observing functional states of the same type of neuron and that these ultrastructural changes occur in response to endocrine manipulation.

Two types of neurons described as ‘pale’ and ‘dark’ were observed within the arcuate nucleus of both the control and experimental female rabbit. Ultrastructurally, these neuron types were identical to those described by other investigators for the rat. It has been suggested that the ‘pale’ and ‘dark’ neurons of this hypothalamic nucleus represent functional states of the same type of cell. However, increases in the ratio of ‘dark’ to ‘pale’ neurons as observed within the arcuate nucleus of the rat following castration, were not seen in the rabbit. Similar findings were also not evident within the arcuate nucleus of the female rabbit following coitus.

As far as could be determined, all neurons of the ventromedial (VMN) nuclei of both the control and experimental rabbit were morphologically identical to the smaller, conventional type neuron. Certainly, ultrastructural changes similar to those observed within the PO and SCH nuclei of the female rabbit following coitus, castration or laparotomy, were never observed.

The basic zonation and subcellular organization of the female rabbit Median Eminence (ME) is similar to that described for other mammalian species. Our EM findings within the external layer of the rabbit ME, however, are not entirely in agreement with the earlier study of Duffy and Menefeef 1965). These investigators reported only one population of DCV within the axon terminals of the rabbit ME external layer. We feel that we have ultrastructural evidence for the presence of at least two distinct populations of DCV within this layer of the rabbit ME. Furthermore, since these vesicle populations occurred within separate axon profiles and terminals, differences in their content and origin are suggested.

Certainly, the relationship between releasing factors (RF) and the various populations of DCV observed within the external layer of the mammalian ME is not well established. The smaller (90 nm - 100 nm) DCV we have observed probably contain the catecholamines, while those of larger (120 nm - 140 nm) diameters may well represent the carriers of the RF associated with gonadotropic activity. The latter view is based primarily on our finding or numerous ‘vesicle ghosts’ within the axon terminals abutting the perivascular space (PVS) of portal capillaries of rabbits sacrificed at 10 minutes post-coitus. The mean diameters of 137±14 nm obtained for these ghosts strongly supports the suggested depletion of only the larger of the two DCV populations. Similar changes were not apparent within the axon terminals containing homogenous populations of only the smaller DCV.

Unquestionably, the precise hypothalamic synthesis sites for the RF associated with control of adenohypophyseal function, continues to provoke comment. From the results obtained from countless studies that have employed a variety of neuroendocrinilogical techniques, two main hypothalamic centers of RF synthesis have been suggested: a) the medial basal hypothalamus (MBH) or hypophysiotropic area (HTA) and b) the anterior hypothalamus. The ultrastructural studies carried out to date within this laboratoiy are in favour of the latter for the following reasons:

1) — the presence of large DCV and ‘vesicle ghosts’ within the external layer of the rabbit ME with diameters similar to those of the large (120-150 nm) DCV synthesized within the PO and SCH nuclei of the same animal in response to coitus, castration and laparotomy.

2) — the absence of evidence for the storage of these large DCV within the somata of PO and SCH nuclei, suggesting their immediate transport toward the ME.

3) — the absence of any ultrastructural changes within neuron somata of the rabbit arcuate nuclei which might reflect enhanced neurosecretory activity in response to coitus and/or castration.

These ultrastructural findings within the rabbit hypothalamus may, therefore, provide the first evidence of a morphological nature for the actual release of RF from their ME storage sites, as well as their synthesis within certain neurons of the anterior hypothalamus.

In its simplest form, the ependyma of the third ventricle consists of a single layer of cuboidal cells. Although these typical mural cells constitute the greater part of the lining of the ventricle, a specialized variety of ependymal cell (the tanycyte) can also be distinguished within circumscribed areas of the ventricular wall. Although such cells are found scattered throughout the dorsoventral extent of the third ventricle, they are particularly numerous along the ventrolateral walls and floor. The regional variation in the surface morphology of the ventricle walls as evident with the scanning electron microscope is consistent with this pattern of tanycyte distribution. Ultrastructural studies have established that the tanycyte is a fundamentally distinct cell with a long basal process extending into the subjacent neuropil and frequently directed toward a capillary wall. This unique morphology conforms closely to its three-dimensional appearance as demonstrated with the scanning electron microscope. The significance of ependymal tanycytes particularly of the third ventricle derives largely from the connections they establish between the ventricular lumen and vasculature of the median eminence. This intriguing structural relationship has led to the suggestion that ependymal cells and cerebrospinal fluid of the third ventricle may be involved in the regulation of adenohypophysial activity. Evidence indicating the functional involvement of specialized ependymal cells in the neuroendocrine control of pituitary activity is reviewed.

In vitro biosynthesis of thyrotropin releasing factor (TRF) by different regions of the hypothalamus of mink was examined. Homogenates of hypothalamic tissue were incubated in Krebs-Ringer medium containing 200 mg% glucose, 10-5M ATP, 0.1 mM histidine and glutamic acid and 0.15 μ c 3H-proline (40 Cilmmol) per mg. tissue. Extraction, purification and estimation of 3H-TRF biosynthesis involved several steps of charcoal extraction, carboxymethylcellulose and sephadex chromatography. 3H-TRF was synthesized throughout the entire antero-posterior extent of the hypothalamus in its dorsal and medial portions. 3H-TRF was synthesized also in a more discreet region, the arcuate nucleus. In vitro biosynthesis of 3H-TRF was stimulated significantly by thyroxine, but not by TSH, estradiol, corticosterone or melatonin. A method is described for collection of cerebrospinal fluid of the third ventricle of the rat brain; TRF concentration in this fluid was approximately in normal animals.

The distribution of TRF-producing cells in the hypothalamus and presence of TRF in cerebrospinal fluid of the third ventricle is discussed with respect to the hypothesis that this releasing factor may be delivered to the median eminence and adenohypophysis in part, via the cerebrospinal fluid.