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PubMed1981

Single-unit activity in the auditory cortex of monkeys actively localizing sound sources: spatial tuning and behavioral dependency.

Single-unit recordings were made from the auditory cortex of unanesthetized rhesus monkeys which were trained to perform a second localization task. Recordings were made from 196 units in 4 animals. Five sound sources were located at 0 degrees (midline) and on either side at azimuths of 37.5 degrees and 75 degrees. Almost most units responded to each of the 5 sources, 49% of the units had peak firing rates for the source on the contralateral side at 75% azimuth. Another 26% of the units had peak firing rates at the 37.5 degrees contralateral location, while only 11% had peak rates for the ipsilateral locations. In order to determine whether the behavior of actively locating a sound source affected units in auditory cortex, response rates compared under two behavioral conditions: one which required the detection of a sound regardless of location and another condition which required identification of a sound's location. of the 196 units, 16 had different response rates for the two conditions, with 15 of the 16 units having higher evoked rates in the localization task. For the 16 units, the difference in firing rate was typically observed for a single speaker location. No correlation could be determined between a unit's location within the subdivisions of auditory cortex and its spatial tuning response properties or its dependency upon behavioral condition.

Animals↗
PubMed1991

Spatial cognition and behavior in young and elderly adults: implications for learning new environments.

Young and elderly women's performances on scene-recognition, distance-ranking, route-execution, and map-placement tasks were compared in familiar and novel supermarkets to seek evidence of an age-related deficit in spatial cognitive performance, a benefit of environmental familiarity, and an age-related decrement in the efficiency of spatial learning. Results suggested that younger adults acquired spatial information in a novel environment more quickly than did elderly adults, but findings indicated neither an age-related deficit in spatial cognitive performance nor a benefit of environmental familiarity. Scores from psychometric tests produced low correlations with cognitive task performance. Of the behaviors observed during exploration and route execution, only 1 was significantly correlated with cognitive task performance. Standing without scanning was negatively correlated with performance on 3 tasks for elderly adults only.

Adult↗
PubMed2004

Behavioral detection of spatial stimuli is reflected in auditory cortical dynamics.

We studied the cortical processing of spatial stimuli by magnetoencephalographic (MEG) measurements using broadband noise bursts presented from eight sound source directions in the horizontal plane. The stimuli were individually created for each subject by using three-dimensional (3D) sound techniques. The subjects carried out a behavioral task where their accuracy for localizing the 3D stimuli was established. We found that the auditory N100m response was sensitive to the sound source direction, exhibiting contralaterally more preponderant responses in both the left and the right hemisphere. Generally, responses were more prominent in the right hemisphere. The behavioral performance of the subjects correlated positively with N100m amplitude organization, showing that the dynamics of auditory cortex predict behavioral sound detection.

Acoustic Stimulation↗
PubMed1996

Brain-behavior relationships: evidence from practice effects in spatial stimulus-response compatibility.

1. We measured relative cerebral blood flow (rCBF) changes with positron emission tomography and H(2) 15O in six normal subjects repeatedly performing a spatial stimulus-response compatibility task. Subjects had two motor response conditions. They were instructed to respond with the left hand to a left visual field light stimulus and with the right hand to a right visual field light stimulus (compatible condition), and with the right hand to a left visual field light stimulus and with the left hand to a right visual field light stimulus (incompatible condition). Six rCBF measurements per condition were performed in each subject. 2. Reaction times were faster (P < 0.0005) in the compatible (287 ms) than the incompatible (339 ms) condition (spatial stimulus-response compatibility effect). A bilateral increase (P < 0.05) in rCBF in the superior parietal lobule of the two hemispheres was observed during the incompatible condition when compared with the compatible one. No rCBF decreases were observed. Reaction times correlated (P < 0.0001) with the rCBF in the two activated superior parietal lobule areas. 3. Reaction times decreased with practice according to a linear trend (P < 0.05). Practice-related linear rCBF increases (P < 0.05) were observed in the dorsolateral prefrontal, premotor, and primary motor cortex of the left hemisphere. No significant rCBF decreases were observed. 4. Practice did not affect the spatial stimulus-response compatibility effect. A parallel shortening of reaction times was observed in both compatible and incompatible conditions, in both left and right hand responses, and in both left and right visual fields. Accordingly, when rCBF was analyzed, the spatial stimulus-response compatibility by practice interaction did not show any significant activated area. 5. These findings suggest that the two activated areas in the left and right superior parietal lobules subserve the mapping of the visual stimulus spatial attributes onto the motor response spatial attributes and that the rCBF increases in the incompatible response condition represent the more complex computational remapping required when stimuli and response do not match spatially. 6. The dorsolateral prefrontal, premotor, and motor rCBF linear increases in the left hemisphere seem to reflect the effect of practice on cortical processes common to both compatible and incompatible response conditions. These cortical processes presumably strengthen the links between stimuli and responses under different stimulus-response compatibility conditions. The lateralization of the rCBF increases suggests a left hemisphere superiority in these processes.

Adult↗
PubMed1992

Amygdala kindling-induced seizures selectively impair spatial memory. 1. Behavioral characteristics and effects on hippocampal neuronal protein kinase C isoforms.

Protein kinase C (PKC) comprises a family of kinases consisting of nine subspecies that are differentially distributed in the central nervous system. This implies distinct functions. Its involvement is suggested in cellular and molecular mechanisms by which the hippocampus exerts influence on information processing. In this study, it was questioned whether abnormal activity in the neuronal substrate, particularly the hippocampal formation, induced by amygdala kindling indeed impairs spatial memory performance and correlated alpha, beta I/II, and gamma PKC subspecies expression. Rats were trained in a spatial discrimination task (SDT) and simultaneously kindled in the amygdala to induce abnormal, epileptiform activity. Control rats were only trained in the holeboard, a "free choice" maze, in which working (WM) and reference memory (RM) were simultaneously examined. Halfway through and at the end of the experiments the influence of kindling and SDT training on the immunoreactivity for PKC subspecies alpha, beta I/II, and gamma was evaluated in the hippocampal formation. Kindling resulted in a gradual increase in afterdischarge duration and motor seizure (MS) severity. Repeated SDT training ultimately resulted in an asymptotic level of WM and RM performance. As soon as generalized MSs developed, kindled rats failed to improve RM, whereas WM was not influenced. Compared to untrained rats, in trained controls PKC gamma but not PKC alpha beta I/II immunoreactivity was elevated in CA1 pyramidal and dentate gyrus granular cells. Generalized but not partial MSs abolished these alterations in PKC gamma immunoreactivity. The present data indicate that repeated training in a SDT affects the expression of PKC subspecies gamma but not of alpha or beta in the rat hippocampus. Generalized epileptiform activity impair both acquisition of new spatial RM information and PKC gamma expression. It is argued that PKC gamma plays a role in cellular mechanisms through which pathological brain activity impairs certain aspects of spatial memory.

Amygdala↗
PubMedDate not supplied

Application timing of complex magnetic fields delineates windows of posttraining-pretesting vulnerability for spatial and motivational behaviors in rats.

Male Wistar rats were trained in a two-session-per-day, non-matching-to-sample radial maze task. During the 2 hr interval between training sessions and testing sessions subjects were exposed for 60 min to either sham fields or to a low intensity (200 to 500 nT) electromagnetic (EM) complex pattern whose electrical (current) equivalent has been shown to elicit long-term potentiation (LTP) in hippocampal slices. This pattern was applied either immediately following the training sessions or immediately antecedent to the testing sessions. Exposures to the experimental field immediately following the training session were associated with an impairment in spatial memory as inferred by increased commissions of reference errors. Exposures immediately prior to the testing session were associated with decreased motivation as inferred by a reduction in speed of responding. These results suggest that the timing of the presentation of patterned magnetic fields may differentially affect the representations of habit strength and drive within the consolidating memory trace.

Analysis of Variance↗
PubMed1998

Effects of interaural decorrelation on neural and behavioral detection of spatial cues.

The detection of interaural time differences (ITDs) for sound localization critically depends on the similarity between the left and right ear signals (interaural correlation). We show that, like humans, owls can localize phantom sound sources well until the correlation declines to a very low value, below which their performance rapidly deteriorates. Decreasing interaural correlation also causes the response of the owl's tectal auditory neurons to decline nonlinearly, with a rapid drop followed by a more gradual reduction. A detection-theoretic analysis of the statistical properties of neuronal responses could account for the variance of behavioral responses as interaural correlation is decreased. Finally, cross-correlation analysis suggests that low interaural correlations cause misalignment of cross-correlation peaks across different frequencies, contributing heavily to the nonlinear decline in neural and ultimately behavioral performance.

Animals↗
PubMed1995

Differential impairments of spatial memory and social behavior in two models of limbic epilepsy.

To explore memory impairments in temporal lobe epilepsy, we used two experimental models in the rats: (a) kainate-induced status epilepticus (SE) resulting in excitotoxic damage and in later spontaneous seizures; and (b) amygdala kindling, known to induce no lesions (or only minor) and neuronal reorganization. Long-term effects of these models on memory were investigated with a spatial learning task in a radial-arm maze, and a social interaction test that implies degree of short-term memory. An histological analysis was made to determine neuronal damage or loss caused by epileptic activity in brain regions that could be related to memory functions. Kainate-induced epilepsy produced large memory deficits in animals tested 5 months after the injection. The rats showed severe lesions in amygdala and hippocampus and piriform and entorhinal cortex. Spatial memory was strongly diminished. The social memory test was severely impaired, probably due to the extent of amygdala injury, which is known to disturb social behavior. On the contrary, kindled rats showed no evident lesion in any brain region and displayed performances as good as those of controls in both tests. These experiments demonstrated that memory deficits appear to be related to the severity of neuronal damage in limbic areas, and the ability to develop seizures (permanence) is not solely responsible for these memory disturbances.

Animals↗
PubMed1993

Disintegration of the spatial organization of behavior in experimental autoimmune dementia.

Experimental autoimmune dementia is a rat model designed to examine the potential role of anti-cholinergic neurons antibodies in neuronal degeneration in dementia and Alzheimer's disease. We have previously shown that sera of patients with Alzheimer's disease contain antibodies which bind specifically to the high molecular weight neurofilament protein of the purely cholinergic electromotor neurons of Torpedo. Production of such antibodies in experimental autoimmune dementia rats by prolonged immunization with the Torpedo cholinergic high molecular weight neurofilament subunit results in accumulation of antibodies in the septum and hippocampus of the immunized rats, in a marked decrease in the density of forebrain cholinergic neurons, and in memory deficits. In the present study we characterized the open-field behavior of experimental autoimmune dementia rats, and examined whether, like in dementia, the spatiotemporal organization of their behavior is impaired. The results obtained revealed that experimental autoimmune dementia rats travel shorter distances; explore a smaller part of the open-field; and perform less round-trips to the key location--the home base--in reference to which their behavior is normally organized. The shrinkage of the explored space and the reduced number of round trips are independent of the amount of locomotion and represent a deterioration in the organization of behavior in time and space. These behavioral changes are specific to the anti-cholinergic immune response of experimental autoimmune dementia rats as they are not observed in rats which were immunized with chemically heterogeneous high molecular weight neurofilament subunit.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1997

Genetic demonstration of a role for PKA in the late phase of LTP and in hippocampus-based long-term memory.

To explore the role of protein kinase A (PKA) in the late phase of long-term potentiation (L-LTP) and memory, we generated transgenic mice that express R(AB), an inhibitory form of the regulatory subunit of PKA, only in the hippocampus and other forebrain regions by using the promoter from the gene encoding Ca2+/ calmodulin protein kinase IIalpha. In these R(AB) transgenic mice, hippocampal PKA activity was reduced, and L-LTP was significantly decreased in area CA1, without affecting basal synaptic transmission or the early phase of LTP. Moreover, the L-LTP deficit was paralleled by behavioral deficits in spatial memory and in long-term but not short-term memory for contextual fear conditioning. These deficits in long-term memory were similar to those produced by protein synthesis inhibition. Thus, PKA plays a critical role in the consolidation of long-term memory.

Amygdala↗
PubMed2004

Tyrosine phosphorylation of caveolin-2 at residue 27: differences in the spatial and temporal behavior of phospho-Cav-2 (pY19 and pY27).

Caveolin-2 is an accessory molecule and the binding partner of caveolin-1. Previously, we showed that c-Src expression leads to the tyrosine phosphorylation of Cav-2 at position 19. To further investigate the tyrosine phosphorylation of Cav-2, we have now generated a novel phospho-specific antibody directed against phospho-Cav-2 (pY27). Here, we show that Cav-2 is phosphorylated at both tyrosines 19 and 27. We reconstituted this phosphorylation event by recombinantly coexpressing c-Src and Cav-2. We generated a series of Cav-2 constructs harboring the mutation of each tyrosine to alanine, singly or in combination, i.e., Cav-2 Y19A, Y27A, and Y19A/Y27A. Recombinant expression of these mutants in Cos-7 cells demonstrated that neither tyrosine is the unique phosphorylation site, and that double mutation of tyrosines 19 and 27 to alanine abrogates Cav-2 tyrosine phosphorylation. Immunofluorescence analysis of NIH 3T3 cells revealed that the two tyrosine-phosphorylated forms of Cav-2 exhibited some distinct properties. Phospho-Cav-2 (pY19) is concentrated at cell edges and at cell-cell contacts, whereas phospho-Cav-2 (pY27) is distributed in a dotlike pattern throughout the cell surface and cytoplasm. Further functional analysis revealed that tyrosine phosphorylation of Cav-2 has no effect on its targeting to lipid rafts, but clearly disrupts the hetero-oligomerization of Cav-2 with Cav-1. In an attempt to identify upstream mediators, we investigated Cav-2 tyrosine phosphorylation in an endogenous setting. We found that in A431 cells, EGF stimulation is sufficient to induce Cav-2 phosphorylation at tyrosines 19 and 27. However, the behavior of the two phosphorylated forms of Cav-2 diverges upon EGF stimulation. First, phospho-Cav-2 (pY19) and phospho-Cav-2 (pY27) display different localization patterns. In addition, the temporal response to EGF stimulation appears to be different. Cav-2 is phosphorylated at tyrosine 19 in a rapid and transient fashion, whereas phosphorylation at tyrosine 27 is sustained over time. Three SH2 domain-containing proteins, c-Src, Nck, and Ras-GAP, were found to associate with Cav-2 in a phosphorylation-dependent manner. However, phosphorylation at tyrosine 27 appears to be more critical than phosphorylation at tyrosine 19 for this binding to occur. Taken together, these results suggest that, in addition to the common characteristics that these two sites appear to share, phospho-Cav-2 (pY19) and phospho-Cav-2 (pY27) may each possess a set of unique functional roles.

Adaptor Proteins, Signal Transducing↗
PubMed1993

Decreased density of forebrain cholinergic neurons and disintegration of the spatial organization of behavior in experimental autoimmune dementia (EAD).

Experimental autoimmune dementia (EAD) is a rat model designed to examine the potential role of anti-cholinergic neurons antibodies (Abs) in the neuropathology of Alzheimer's disease (AD) and dementia. We have previously shown that sera of AD and Down's syndrome patients contain Abs which bind specifically to the high molecular weight neurofilament protein (NF-H) of the purely cholinergic electromotor neurons of Torpedo. Production of such Abs in EAD rats by prolonged immunization with Torpedo cholinergic NF-H results in the accumulation of IgG in the septum and hippocampus of the immunized rats and in memory deficits. In the present study, we examined immunohistochemically whether the anti-cholinergic NF-H immune response of the EAD rats affects their brain cholinergic neurons. In addition, since dementia is associated with severe deterioration in the spatio-temporal organization of behavior, we examined whether EAD rats also mimic this important feature of dementia. The results obtained show that production in EAD rats of anti-cholinergic NF-H Abs similar to those found in AD patients results in a marked decrease in the density of forebrain cholinergic neurons and in derangements in the spatio-temporal organization of their behavior. These findings may replicate pathogenic processes in AD and support a role for anti-cholinergic NF-H Abs in the degeneration of cholinergic neurons in the disease.

Animals↗