Study of the ancient tecto-thalamo-cortical pathway of the visual system in rats

Recording the evoked potentials and neuronal activity, electrophysiological studies have been made on tecto-thalamo-cortical tract in rats. The existence of a system of efferent projections in the superficial, visual layers of the superior colliculi was shown which are diffusely present in the nucleus lateralis posterior (n. LP), indicating low level of morpho-functional organization of this region of the dorsal thalamus in rats. In response to electrical stimulation of the n. LP, in laterocaudal parts of the visual system (fields 17 and 18a of the cortex) the evoked potentials of primary-negative polarity were observed which are associated mainly with the superficial (I--IV) cortical layers. Predominant representation of tecto-thalamo-cortical system in the laterocaudal visual area of the cortex indicates the tendency to separate representation (with respect to cortical areas and cortical layers) of retino-geniculate and retino-tecal visual systems in rats.     

Effects of Fetal Treatment with Methylazoxymethanol acetate at Various Gestational Dates on the Neurochemistry of the Adult Neocortex of the Rat

The effects of gestational date (13, 14, 15, and 17 days) of administration of methylazoxymethanol acetate (20 mg/kg) on the cortical synaptic chemistry and morphology of the rat has been examined in adult offspring. Treatment at 13 days of gestation (DG) resulted in cortical hypoplasia that affected primarily the deep layers whereas treatment at 14 and 15 days gestation caused a severe hypoplasia of cortical neurons above layer V and a 66 to 77% reduction in cortical mass. The 17-DG treatment caused only a 20% reduction in cortical weight with effects apparent only in the superficial layers. At no treatment date did the specific activity of glutamate decarboxylase differ significantly from control. In contrast, presynaptic markers for noradrenergic (tyrosine hydroxylase and norepinephrine) and for serotonergic (serotonin) terminals were increased in concentration in direct proportion to the degree of cortical hypoplasia. The specific activity of choline acetyltransferase was significantly increased at all treatment dates but total activity per cortical slab was significantly reduced on treatment days 13–15.     

Glutamate dehydrogenase activity in motor cortex neurons during restoration of disrupted visual function]

The recovery of the visual function of rats throughout two weeks after deprivation period (keeping animals in dark chambers for 8 weeks from their birth) leads to a significant normalization of the activity level of glutomatedehydrogenase in the neurones of the III and V layers of the motor cortex. The changes of the enzyme activity in the neurones are accompanied by a diminution of their sizes. The obtained data together with the results of the previous studies (Busnuk, 1976), suggest that the elimination of the visual impulse activity in the early ontogenesis exerts a specific and reversible influence on the morpho-chemical differentiation of neurones both in the visual and in the motor cortical areas. The functional factors determining the direction of changes in the studied parameters of cortical neurones during deprivation and in the rate of their normalization during recovery of the visual function are discussed.     

Cortical upper layer neurons derive from the subventricular zone as indicated by Svet1 gene expression

The cerebral cortex is composed of a large variety of different neuron types. All cortical neurons, except some interneurons, are born in two proliferative zones, the cortical ventricular (VZ) and subventricular (SVZ) zones. The relative contribution of both proliferative zones to the generation of the diversity of the cortical neurons is not well understood. To further dissect the underlying mechanism, molecular markers specific for the SVZ are required. Towards this end we performed a subtraction of cDNA libraries, generated from E15.5 and E18.5 mouse cerebral cortex. A novel cDNA, Svet1, was cloned which was specifically expressed in the proliferating cells of the SVZ but not the VZ. The VZ is marked by the expression of the Otx1 gene. Later in development, Svet1 and Otx1 were expressed in subsets of cells of upper (II-IV) and deep (V-VI) layers, respectively. In the reeler cortex, where the layers are inverted, Svet1 and Otx1 label precursors of the upper and deeper layers, respectively, in their new location. Interestingly, in the Pax6/small eye mutant, Svet1 activity was abolished in the SVZ and in the upper part of the cortical plate while the Otx1 expression domain remained unchanged. Therefore, using Svet1 and Otx1 as cell-type-specific molecular markers for the upper and deep cortical layers we conclude that the Sey mutation affects predominantly the differentiation of the SVZ cells that fail to migrate into the cortical plate. The abnormality of the SVZ coincides with the absence of upper layer cells in the cortex. Taken together our data suggest that while the specification of deep cortical layers occurs in the ventricular zone, the SVZ is important for the proper specification of upper layers.     

Prior expectations evoke stimulus-specific activity in the deep layers of the primary visual cortex

The way we perceive the world is strongly influenced by our expectations. In line with this, much recent research has revealed that prior expectations strongly modulate sensory processing. However, the neural circuitry through which the brain integrates external sensory inputs with internal expectation signals remains unknown. In order to understand the computational architecture of the cortex, we need to investigate the way these signals flow through the cortical layers. This is crucial because the different cortical layers have distinct intra- and interregional connectivity patterns, and therefore determining which layers are involved in a cortical computation can inform us on the sources and targets of these signals. Here, we used ultra-high field (7T) functional magnetic resonance imaging (fMRI) to reveal that prior expectations evoke stimulus-specific activity selectively in the deep layers of the primary visual cortex (V1). These findings are in line with predictive processing theories proposing that neurons in the deep cortical layers represent perceptual hypotheses and thereby shed light on the computational architecture of cortex.

The way we perceive the world is strongly influenced by our expectations, but the neural circuitry through which the brain achieves this remains unknown. A study using ultra-high field fMRI reveals that prior expectations evoke stimulus-specific signals in the deep layers of the primary visual cortex.     

Angiotensin converting enzyme inhibition blocks interstitial hyaluronan dissipation in the neonatal rat kidney via hyaluronan synthase 2 and hyaluronidase 1

A functional renin-angiotensin system (RAS) is required for normal kidney development. Neonatal inhibition of the RAS in rats results in long-term pathological renal phenotype and causes hyaluronan (HA), which is involved in morphogenesis and inflammation, to accumulate. To elucidate the mechanisms, intrarenal HA content was followed during neonatal completion of nephrogenesis with or without angiotensin converting enzyme inhibition (ACEI) together with mRNA expression of hyaluronan synthases (HAS), hyaluronidases (Hyal), urinary hyaluronidase activity and cortical lymphatic vessels, which facilitate the drainage of HA from the tissue. In 6-8 days old control rats cortical HA content was high and reduced by 93% on days 10-21, reaching adult low levels. Medullary HA content was high on days 6-8 and then reduced by 85% to 12-fold above cortical levels at day 21. In neonatally ACEI-treated rats the reduction in HA was abolished. Temporal expression of HAS2 corresponded with the reduction in HA content in the normal kidney. In ACEI-treated animals cortical HAS2 remained twice the expression of controls. Medullary Hyal1 increased in controls but decreased in ACEI-treated animals. Urine hyaluronidase activity decreased with time in control animals while in ACEI-treated animals it was initially 50% lower and did not change over time. Cells expressing the lymphatic endothelial mucoprotein podoplanin in ACEI-treated animals were increased 18-fold compared to controls suggesting compensation. In conclusion, the high renal HA content is rapidly reduced due to reduced HAS2 and increased Hyal1 mRNA expressions. Normal angiotensin II function is crucial for inducing these changes. Due to the extreme water-attracting and pro-inflammatory properties of HA, accumulation in the neonatally ACEI-treated kidneys may partly explain the pathological renal phenotype of the adult kidney, which include reduced urinary concentration ability and tubulointerstitial inflammation.     

Bicarbonate-activated ATPase activity in renal cortex of chronically acidotic rats.

The effect of chronic NH4Cl-induced acidosis on the activity of a bicarbonate-activated component of ATPase was studied in homogenates of renal tissue from Wistar rats. This particular component of ATPase, which is maximally stimulated by 50 mM bicarbonate, and is insensitive to the action of ouabain, has been implicated in the active transport of bicarbonate in various tissues. The activity of this enzyme in cortical homogenates from an acidotic group of animals was 4.3 +/- 0.4 mumol Pi/mg protein per hour compared with 5.8 +/- 0.3 mumol Pi/mg protein per hour in a control group (p less than 0.02). No significant change in bicarbonate ATPase activity was observed in medullary homogenates, and NaK-ATPase activity remained the same in cortex and medulla of both groups. Subcellular fractionation of the cortical tissue homogenates revealed that bicarbonate ATPase activity in a microsomal fraction from acidotic animals was 6.5 +/- 1.1 mumol Pi/mg protein per hour compared with 9.4 +/- 1.2 mumol Pi/mg protein per hour in control animals (p less than 0.02). Bicarbonate ATPase activity in other subcellular fractions was not different in the two groups of animals. These findings are compatible with the hypothesis that a certain percentage of bicarbonate reabsorption in the nephron is mediated by a bicarbonate-activated component of ATPase.     

EFFECT OF COPPER STATUS ON BRAIN NEUROTRANSMITTER METABOLISM IN THE LAMB

Abstract— Ataxic and non-ataxic lambs reared under field conditions which gave rise to low copper status were treated with copper intravenously. Untreated ataxic animals served as controls. The neurotransmitter amines, dopamine, norepinephrine and serotonin, were determined in the anterior and posterior regions of the brain stem. Dopamine levels in the anterior region, including the corpus striatum, were significantly lower in the untreated animals than in those treated with copper. Norepinephrine levels were also lower but serotonin concentrations were not different. Plasma amine oxidase activity was markedly higher in the copper treated animals but monoamine oxidase activity in brain stem homogenates was not significantly affected. The monoamine oxidase activity in cortical and cerebellar homogenates was significantly lower in the treated animals than in the untreated animals.     

Effects of low-potassium diet on N-ethylmaleimide-sensitive ATPase in the distal nephron segments.

The present study was undertaken to investigate whether or not potassium deficiency influences N-ethylmaleimide (NEM)-sensitive ATPase in the distal nephron segments of the rat. One group of animals was fed a low-K diet, whereas the normal K-group was given the same diet after supplementation with KCl. The nephron segments examined were: the medullary and cortical thick ascending limbs, the distal convoluted tubule, and the cortical, outer and inner medullary collecting ducts. NEM-sensitive ATPase activity in microdissected segments was measured by a fluorometric microassay. The plasma K+ concentration in the low-K group was 3.1 +/- 0.3 mEq/l compared with 4.2 +/- 0.1 mEq/l in the normal-K group. NEM-sensitive ATPase activity in the outer medullary collecting duct of low-K diet animals was significantly greater than in normal-K animals. There was no significant difference in NEM-sensitive ATPase activity between the two groups of animals in the other nephron segments examined. It is suggested that NEM-sensitive H-ATPase activity in the outer medullary collecting duct is modulated by the potassium status of the animal.     

Postnatal morphological changes in neurons and glial cells in neocortex of mice developing at the background of serotonin deficit

It has been shown that deficit of serotonin during embryogenesis in rodents is accompanied by changes of morphological characteristics of neurons and glial cells at the period of postnatal development. A characteristic peculiarity of these changes is cell vacuolization that is of different expression in various cortical layers. In the experimental animals as compared with control ones, neurons of all neocortex layers have changed nuclei and a reduced volume of the cytoplasm. In neurons of upper layers, nuclei and cytoplasm contain occasional small vacuoles. In deep layers, vacuolization both of nuclei and of the cytoplasm is expressed to the much greater degree and vacuoles of large size are predominant. Results of immunocytochemical study have shown that in animals developing at the background of serotonin deficit there takes place a delay of the rates of formation and differentiation of astrocytic glia.     

The influence of cortical lesions on penicillin induced convulsive activity in the awake rat

1. Experiments were performed to investigate the effects of cortical lesions on convulsive behaviour. Rats were lesioned in the left motor or sensory cortex by aspirating cortical tissue 2 to 3 months prior to the elicitation of convulsions. Convulsions were induced in the awake rats by the GABA antagonist Na-penicillin (Na-PCN) which was applied into the superficial layer of the foreleg field of their right motor cortex. Convulsive activity was recorded by means of the EEG. 2. The time courses of convulsive cortical activity were similar in the animals without or with a cortical lesion. Generalized seizures belonged to the tonic-clonic type in both intact and lesioned rats. 3. The early period of convulsive activity was described by the time to the onset (latency) of the first convulsive potential, jerk and seizure, and by the mean repetition rate of jerks during the first ten minutes, and the duration of the first generalized seizure. None of these parameters was significantly affected by a cortical lesion. 4. The median duration of the convulsive activity in intact animals was 162 min. In rats with a lesion in the sensory cortex it raised to more than 540 min while a lesion of the motor cortex increased the median duration to more than 273 min. The differences between intact and lesioned rats were significant (p less than 0.01 and p = 0.05, respectively). 5. The median time to the onset of the last generalized seizure in intact rats corresponded to 92 min with respect to the time of Na-PCN application. In rats with a lesion of the sensory cortex the last seizure was generated 433 min and in animals with a lesion of the motor cortex 167 min after Na-PCN treatment of the motor cortex of one side. This increase of latency of the last seizure was significant for the rats with a lesioned sensory area (p less than 0.02) or motor area (p = 0.05) compared to that of the intact rats. Additionally, the number of generalized seizures was significantly (p less than 0.01) increased by both groups of rats with a lesion of the motor or sensory cortex. 6. It is suggested that a substantial lesion of the cortex decreases predominantly the intrinsic cortical inhibition thus destabilizing brain function. This destabilizing effect becomes pronounced under the condition of superimposed suppression of the GABAergic cortical component. It is concluded that the intrinsic cortical inhibitory mechanism which in the intact brain acts against hyperexcitation and prevents the development of neuronal synchronization, i.e. the formation of seizures, becomes less effective in performing this task once an abnormal brain activation has developed.     

Evidence for Synchronous Activation of Neurons Located in Different Layers of Primary Somatosensory Cortex

Although many studies have examined the columnar organization of primary somatosensory (SI) cortex, the functional relationship among neurons in different layers remains unclear. To understand how activity is coordinated among different cortical layers, the present investigation tested the hypothesis that the initial part of a peripheral stimulus produces a serial pattern of laminar activation in SI cortex. Extracellular discharges of 334 histologically recovered neurons were recorded from the medial bank of the coronal sulcus in nine anesthetized cats during electrical or cutaneous stimulation of the distal forelimb. Mean responses during the initial 50-msec period following stimulus onset were largest in layers IIIb or IV for both types of stimulation, but laminar differences in the magnitude of onset responses were not statistically significant. Among 175 neurons with responses exceeding 0.5 spikes per stimulus, electrical Stimulation consistently produced shorter response latencies than mechanical indentation in the extragranular (II, IIIa, V, VI), but not in the middle (IIIb, IV), cortical layers. The average minimum latencies for different cortical layers ranged from 7.4 to 10.1 msec for responses to electrical stimulation and from 10.3 to 11.6 msec for responses to mechanical indentations, but these laminar differences were not statistically significant. In some experiments, neurons in different layers of a cortical column were recorded simultaneously with dual-electrode assemblies; among 37 neuron pairs in which both neurons responded with more than 0.5 spikes per stimulus, response latencies were similar, even though the neurons were separated by several hundred microns. Cross-correlation analysis of the onset responses for neurons recorded simultaneously from different layers also indicated that many cells throughout a cortical column were activated nearly simultaneously by the initial phase of a peripheral stimulus. Results from the present study are compared with previous reports examining laminar patterns of activation.     

Postnatal changes of morphology of nerve and glial cells in neocortex of mice developing on the background of serotonin deficit

It has been shown that deficit of serotonin during embryogenesis in rodents is accompanied by changes of morphological characteristics of neurons and glial cells at the period of postnatal development. A characteristic peculiarity of these changes is cell vacuolization that is of different expression in various cortical layers. In the experimental animals as compared with control ones, neurons of all neocortex layers have changed nuclei and a reduced volume of the cytoplasm. In neurons of upper layers, nuclei and cytoplasm contain occasional small vacuoles. In deep layers, vacuolization both of nuclei and of the cytoplasm is expressed to the much greater degree and vacuoles of large size are predominant. Results of immunocytochemical study have shown that in animals developing on the background of serotonin deficit there takes place a delay of the rates of formation and differentiation of astrocytic glia.     

Effects of Chronic Ethanol Treatment on the β-Adrenergic Receptor-Coupled Adenylate Cyclase System of Mouse Cerebral Cortex

Chronic ingestion of ethanol, which produced tolerance and physical dependence, resulted in altered function of the cerebral cortical beta-adrenergic receptor-coupled adenylate cyclase system in mice. Although there was no change in basal adenylate cyclase activity, or in the activity of the digitonin-solubilized catalytic unit, stimulation of adenylate cyclase activity by the nonhydrolyzable guanine nucleotide analog guanylylimidodiphosphate [Gpp(NH)p] was reduced in brains of ethanol-fed animals. Ethanol added in vitro increased adenylate cyclase activity, and this enhancement, in the presence of Gpp(NH)p, was also reduced in cortical membranes of ethanol-fed mice. Furthermore, the maximal response to isoproterenol was decreased, and the EC50 for isoproterenol stimulation of adenylate cyclase activity was increased in ethanol-fed animals. The results are consistent with a qualitative or quantitative defect in the function of the stimulatory guanine nucleotide-binding protein (Ns), as well as in the beta-adrenergic receptor, after chronic ethanol exposure. In part, these changes appear to be similar to those that occur during heterologous desensitization of various receptor systems, and may be associated with dependence on or tolerance to ethanol.     

Development and plasticity of cortical areas and networks

The development of cortical layers, areas and networks is mediated by a combination of factors that are present in the cortex and are influenced by thalamic input. Electrical activity of thalamocortical afferents has a progressive role in shaping cortex. For early thalamic innervation and patterning, the presence of activity might be sufficient; for features that develop later, such as intracortical networks that mediate emergent responses of cortex, the spatiotemporal pattern of activity often has an instructive role. Experiments that route projections from the retina to the auditory pathway alter the pattern of activity in auditory thalamocortical afferents at a very early stage and reveal the progressive influence of activity on cortical development. Thus, cortical features such as layers and thalamocortical innervation are unaffected, whereas features that develop later, such as intracortical connections, are affected significantly. Surprisingly, the behavioural role of 'rewired' cortex is also influenced profoundly, indicating the importance of patterned activity for this key aspect of cortical function.     

Laminar distribution of benzodiazepine receptors in visual cortex of adult rat

The characteristics and distribution of benzodiazepine receptors in individual layers of the visual cortex of adult rats were examined with the 3H-flunitrazepam binding technique employed on intact tissue slices. The different visual cortical layers were separated by cutting serial cryocut sections horizontally to the cortical surface and collecting the slices from each individual cortical layer under anatomical control. Highest benzodiazepine receptor densities were found in layers IV and VI. A moderate receptor density was detected in layer V (80% of highest density). The lowest receptor binding was observed in cortical layers I and II/III, still representing 66% of the highest receptor density. Binding affinities varied slightly between layers with dissociation constants somewhat higher for layers IV to VI in comparison to layers I and II/III. The distinct laminar pattern of benzodiazepine receptors in rat visual cortex suggests a differential neuromodulatory significance of these receptors in each individual cortical layer.     

The effect of dexphenmetrazine and acetyldexphenmetrazine upon epileptic electrographic activities in the brain of the turtle.

The effect of acetyldexphenmetrazine (ADP) and dexphenmetrazine (DP) on normal and epileptic electrographic activities in the cortical and thalamic structures of the turtle brain were studied in curarized and artificially ventilated animals. Both drugs almost exclusively influenced cortical activities. The effect of low doses of ADP and DP was similar--they desynchronized cortical activity and suppressed the activity of a cortical penicillin focus. They also elevated the cortical response to optic stimuli. Higher doses of ADP continued to suppress both normal and epileptic cortical activities. Higher doses of DP had a two phase effect with enhancement of epileptic activity in the first phase. Continuous trains of theta activity appeared after low doses of ADP and very often after both low and high doses of DP. The findings are discussed in terms of comparative physiology of the brain.     

Effect of phenobarbital on cortical epileptogenic foci in the rat

The activity of epileptogenic foci was studied in acute experiments on adult male rats without general anaesthesia; the animals first received an intraperitoneal injection of phenobarbital [40 mg/kg] and 30 min later a cortical focus was induced by the local application of penicillin. These foci, which were induced in the sensorimotor area, had a lower discharge frequency than in the controls and the formation of projected discharges was delayed. In two symmetrical and asymmetrical cortical foci, activity was synchronized significantly more slowly after phenobarbital than in the controls. The cortical interhemispheric response was not influenced by the administered dose of phenobarbital. In these experiments, phenobarbital had an anti-epileptic effect both on the primary focus and on the spread of epileptic activity from this focus.     

Stochastic emergence of repeating cortical motifs in spontaneous membrane potential fluctuations in vivo

It was recently discovered that subthreshold membrane potential fluctuations of cortical neurons can precisely repeat during spontaneous activity, seconds to minutes apart, both in brain slices and in anesthetized animals. These repeats, also called cortical motifs, were suggested to reflect a replay of sequential neuronal firing patterns. We searched for motifs in spontaneous activity, recorded from the rat barrel cortex and from the cat striate cortex of anesthetized animals, and found numerous repeating patterns of high similarity and repetition rates. To test their significance, various statistics were compared between physiological data and three different types of stochastic surrogate data that preserve dynamical characteristics of the recorded data. We found no evidence for the existence of deterministically generated cortical motifs. Rather, the stochastic properties of cortical motifs suggest that they appear by chance, as a result of the constraints imposed by the coarse dynamics of subthreshold ongoing activity.