We report the histological, ultrastructural, and immunocytochemical features of six hypothalamic gangliocytomas associated with pituitary GH cell adenomas and/or acromegaly. In four patients, the gangliocytoma was intrasellar, and no hypothalamic investigation was performed; in two patients, autopsy confirmed hypothalamic involvement. Four patients had a gangliocytoma associated with pituitary GH cell adenoma and acromegaly; electron microscopy demonstrated an intimate association between neurons and adenomatous GH cells. One patient had a gangliocytoma and a GH cell adenoma but no clinical evidence of acromegaly. In the sixth patient, clinical and biochemical acromegaly was manifest, but no pituitary adenoma was demonstrated. Using immunocytochemistry, human pancreatic tumor GRF (hptGRF-40) was localized in the majority of neurons of all six gangliocytomas. The pituitary adenomas and nontumorous adenohypophyses were negative for hptGRF-40. In addition, somatostatin, glucagon, and GnRH were demonstrated within some neurons of several tumors; insulin and gastrin stains were equivocal. These findings confirm previous proposals of production of a GRF by such gangliocytomas. While the significance of other peptides found in some of the tumors is uncertain, the presence of hptGRF-40 in neurons of these gangliocytomas supports the theory that GRF excess is the mechanism responsible for over-production of GH and provides evidence for a syndrome of hypothalamic acromegaly.

The phenomenon of paired-pulse facilitation (PPF) was exploited to investigate the role of presynaptic mechanisms in the induction and maintenance of long-term synaptic plasticity in the neocortex. Long-term potentiation (LTP) and depression (LTD) were induced without afferent activation by applying tetani of intracellular pulses. Our results show that synaptic modifications closely resembling LTP and LTD can be induced by postsynaptic activation alone. The polarity of these synaptic modifications depends on initial properties of the input, as indicated by a correlation between initial PPF ratio and post-tetanic amplitude changes: inputs exhibiting strong PPF, which might be associated with low release probability tend to be potentiated, while inputs with small PPF are more likely to show depression. Maintenance of both LTP and LTD involve presynaptic mechanisms, as indicated by changes in PPF ratios and in failure rate after LTP or LTD induction. Presynaptic mechanisms could include changes in release probability and/or in the number of active release sites. Because induction was postsynaptic, this supports the notion of a retrograde signal. The relative contribution of pre- and postsynaptic mechanisms in the maintenance of long-term synaptic modifications depends on the initial state of the synaptic input and on LTP magnitude. PPF changes were especially pronounced in inputs which had initially high PPF and underwent strong potentiation. Since LTP and LTD are associated with changes of PPF ratios these synaptic modifications do not only alter the gain but also the temporal properties of synaptic transmission. Because of the LTP associated reduction of PPF, potentiated inputs profit less from temporal summation, favouring transmission of synchronized, low frequency activity.

The cat dorsal lateral geniculate nucleus (LGN) was examined at the light- and electron-microscopic level after immunocytochemistry for GAD (the synthesizing enzyme of the inhibitory neurotransmitter GABA), to identify cells and processes with GAD-like immunoreactivity. GAD-positive perikarya were distributed throughout the A and C laminae, constituting a moderate proportion of cells in the LGN. Labeled cells were characterized by small size, scant cytoplasm, relatively large nuclei with common indentations, small mitochondria, few organelles and few strands of rough endoplasmic reticulum. Unlabeled cells were of large, medium and small size. GAD-positive terminals were identified as F1 and F2 types (Guillery's nomenclature) on the basis of their synaptic relations and ultrastructure. Labeled F2 terminals were postsynaptic to retinal (RLP) boutons and presynaptic to unlabeled dendrites in synaptic glomeruli. Labeled F1 terminals made synapses on unlabeled somata and dendrites, and on labeled dendrites and F2 terminals. Presumably, most labeled F1 terminals originate from GABAergic perigeniculate axons. Retinal (RLP) and cortico-geniculate (RSD) boutons remained unlabeled in the reactive zone. These terminals made synapses with labeled and unlabeled dendrites and with labeled F2 boutons. In conjunction with previous studies on GAD-positive cells in the perigeniculate nucleus, these results provide immunocytochemical and morphological evidence suggesting that the GABAergic intrinsic and extrinsic (perigeniculate) interneurons mediate the different inhibitory phenomena which occur in relay cells of the cat LGN. The ultrastructural features and synaptic relations of GABAergic cells and processes in the cat LGN are similar to those of equivalent neural elements in the LGN of rat and monkey, suggesting general principles of organization and morphology for GABAergic neurons in the thalamus of different mammals.

The neuronal composition of callosally projecting cells in cat visual cortex was determined with a combination of retrograde labelling and intracellular injection. Fluorescent tracers were stereotaxically injected into the proximity of the area 17/18 border, corresponding to the representation of the visual vertical meridian. In fixed slice preparations of homotopic regions of the contralateral hemisphere retrogradely labelled cells were filled with Lucifer Yellow. Of more than a hundred injected cells a morphological variety of pyramidal cells, located in cortical layers II-IV and VI, constituted the prevalent cell class in the contralateral projection. A minor proportion of spiny stellate cells was encountered in layer IV. Despite the presence of a contralaterally projecting smooth stellate cell, presumed to be a basket cell, it is concluded that the efferents to contralateral visual cortex predominantly arise from pyramidal and spiny stellate cells. Thus, in agreement with findings from anterograde degeneration studies, the interhemispheric pathway most likely conveys a direct excitatory input to postsynaptic target cells.

Ocular dominance (OD) columns in the cat visual cortex were visualized with autoradiography after intravitreal injection of (3H)proline. Extending previous studies, a flat-mount technique was applied that enabled the analysis of the distribution of label throughout extensive regions of the visual cortex without requiring reconstruction from serial sections. OD-columns were confined to layer IV and consisted of isolated patches and short bands. The latter were parallel to each other and regularly spaced, the main trajectory being orthogonal to the 17/18 border. This pattern of the geniculo-cortical terminals was similar in the hemispheres ipsi- and contralateral to the injected eye. The mean periodicities of the OD-bands were virtually identical in the two hemispheres of the same animal: 850 microns and 830 microns in cat D1 and 770 microns and 800 microns in cat D2. However, the ipsilateral OD-columns appeared smaller, more heavily labeled and more sharply delineated than the contralateral columns.