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L deToledo-Morrell

Publications and source records attributed to L deToledo-Morrell.

At least 19 recordsLinked to original sources
PubMed2005

MRI predictors of risk of incident Alzheimer disease: a longitudinal study.

OBJECTIVE: To determine if baseline entorhinal and hippocampal volumes and their rate of atrophy could predict the risk of incident Alzheimer disease (AD). METHODS: The authors used proportional odds models to assess the relationship between entorhinal and hippocampal size and risk of incident AD among 58 nondemented elderly people. All participants were followed with annual clinical evaluations and structural MRI scans for up to 5 years (baseline and 5 years of follow-up). At baseline, 23 of 58 participants received a diagnosis of amnestic mild cognitive impairment (MCI) and 35 of 58 were healthy control subjects with no cognitive impairment. Structural MRI scans were acquired with a T1-weighted three-dimensional spoiled gradient-recalled echo pulse sequence in a 1.5 T scanner. Entorhinal and hippocampal volumes were derived from 1.6-mm gapless coronal images reformatted to be perpendicular to the long axis of the hippocampus and were normalized by dividing with intracranial volume. RESULTS: Fourteen of 58 nondemented participants developed AD during the follow-up period. Initial diagnosis of MCI was a significant predictor of incident AD. In addition, both baseline entorhinal volume and its slope of decline were independent predictors of incident AD, but initial hippocampal size and its rate of decline were not, after controlling for entorhinal volume. CONCLUSION: In nondemented individuals, entorhinal cortex atrophy is associated with risk of Alzheimer disease.

Aged↗
PubMed2005

Spatial memory in aged rats is related to PKCgamma-dependent G-protein coupling of the M1 receptor.

In the present study, individual differences in spatial memory in aged Fischer 344 (F344) rats were associated with the extent of G-protein coupling of the M1 muscarinic receptor and the dendritic-to-somal ratio of hippocampal PKCgamma (d/sPKCgamma) immunogenicity. Following testing in the eight-arm radial maze task, 7 young and 13 aged rat brains were sectioned through the dorsal hippocampal formation (HF). G-protein coupling of the M1 receptor was assessed autoradiographically using competition binding studies in the presence and absence of a G-protein uncoupler to determine high (K(H)) and low (K(L)) affinity states for agonist in the HF, neocortex, and amygdala. In aged animals, a relationship between choice accuracy in the maze and K(H), a measure of M1 receptor-G-protein coupling was seen in the dentate gyrus, CA3, CA1, and neocortex. Furthermore, choice accuracy and d/sPKCgamma immunogenicity showed a significant relationship in CA1. Lastly, a correlation was seen in the CA1 of aged animals between K(H) and d/sPKCgamma. These relationships did not hold for the amygdala. Thus, individual differences in a naturally occurring age-dependent disruption of cholinergic-PKCgamma signal transduction is associated with spatial memory dysfunction.

Age Factors↗
PubMed1995

Tailored anterior temporal lobectomy. Relation between extent of resection of mesial structures and postsurgical seizure outcome.

OBJECTIVE: The purpose of this study was to assess the relationship between the extent of resection of mesial temporal structures and postsurgical seizure outcome in a group of patients who had undergone a tailored anterior temporal lobectomy. METHODS: Twenty-four patients with unilateral interictal and ictal foci restricted to anterior/mesial temporal regions underwent resection of mesial and temporal lateral structures, the extent of which was tailored by intraoperative electrocorticographic findings and functional mapping of eloquent cortex. The extent of resection was determined with postoperative magnetic resonance imaging scans, using a semiquantitative method, based on a 20-compartment model of the temporal lobe. The magnetic resonance imaging scans were rated by three investigators blinded to seizure outcome. Follow-up period ranged between 18 months and 5 years. RESULTS: Amygdala and hippocampus were spared in six patients; nine patients had a partial to total resection of amygdala, eight patients had a resection of amygdala and the anterior third of the hippocampus, and one patient underwent resection of amygdala and anterior two thirds of hippocampus. Twenty-one of the 24 patients were seizure free (Engel's class I) and three had rare seizures (Engel's class II). Among these three patients, one had a resection of amygdala; one had resection of amygdala and anterior third of hippocampus; while in the third patient, mesial structures were spared. CONCLUSION: These data suggest that in patients with an anterotemporal seizure focus, the sparing or limited resection of amygdala and/or hippocampus is not necessarily associated with a poor seizure outcome, as had been previously suggested, provided that the decision not to resect is based on the absence of epileptiform activity during intraoperative electrocorticography or during recordings with depth electrodes.

Adolescent↗
PubMed1993

Structural synaptic correlate of long-term potentiation: formation of axospinous synapses with multiple, completely partitioned transmission zones.

Synapses were analyzed in the middle molecular layer (MML) and inner molecular layer (IML) of the rat dentate gyrus following the induction of long-term potentiation (LTP) by high-frequency stimulation of the medial perforant path carried out on each of 4 consecutive days. Potentiated animals were sacrificed 1 hour after the fourth high frequency stimulation. Stimulated but not potentiated and implanted but not stimulated animals served as controls. Using the stereological disector technique, unbiased estimates of the number of synapses per postsynaptic neuron were differentially obtained for various subtypes of axospinous junctions: For atypical (giant) nonperforated synapses with a continuous postsynaptic density (PSD), and for perforated ones distinguished by (1) a fenestrated PSD and focal spine partition, (2) a horseshoe-shaped PSD and sectional spine partition, (3) a segmented PSD and complete spine partition(s), and (4) a fenestrated, (5) horseshoe-shaped, or (6) segmented PSD without a spine partition. The major finding of this study is that the induction of LTP in the rat dentate gyrus is followed by a significant and marked increase in the number of only those perforated axospinous synapses that have multiple, completely partitioned transmission zones. No other synaptic subtype exhibits such a change as a result of LTP induction. Moreover, this structural alteration is limited to the terminal synaptic field of activated axons (MML) and does not involve an immediately adjacent one (IML) that was not directly activated by potentiating stimulation. The observed highly selective modification of synaptic connectivity involving only one particular synaptic subtype in the potentiated synaptic field may represent a structural substrate of the long-lasting enhancement of synaptic responses that characterizes LTP.

Animals↗
PubMed1992

Increase in the number of axospinous synapses with segmented postsynaptic densities following hippocampal kindling.

Kindling results from intermittent electrical stimulation of a local brain region and leads to a virtually permanent augmentation of synaptic responsiveness in the stimulated circuit. It has been hypothesized that an increase in the number of synapses may represent a structural basis for the enduring expression of synaptic plasticity following kindling, but such an alteration has not been demonstrated unequivocally. The present report provides evidence that hippocampal kindling is indeed accompanied by an increase in synaptic numbers. Young adult rats were kindled via medial perforant path stimulation and sacrificed 4 weeks after reaching a criterion of 5 generalized seizures. Stimulated but not kindled and implanted but not stimulated rats served as controls. Synapses were analyzed in the middle (MML) and inner (IML) molecular layer of the hippocampal dentate gyrus. Using the stereological disector technique, unbiased estimates of the number of synapses per neuron were differentially obtained for 3 morphological subtypes of perforated axospinous synapses characterized by a fenestrated, horseshoe-shaped or segmented postsynaptic density (PSD). A significant increase in synaptic numbers was found to selectively involve only those perforated synapses which are distinguished by a segmented PSD consisting of 2-5 discrete plates. This structural modification was restricted to the terminal synaptic field of stimulated axons (MML), but was not observed in an immediately adjacent synaptic field (IML) which was not directly stimulated during kindling. Since synapses distinguished by a segmented PSD may represent specialized synaptic contacts of an unusually high efficacy, a selective increase in their numbers is likely to provide a structural substrate of the augmented synaptic gain associated with kindling.

Animals↗
PubMed1992

Age-related loss of axospinous synapses formed by two afferent systems in the rat dentate gyrus as revealed by the unbiased stereological dissector technique.

Previous attempts to elucidate whether a loss of hippocampal synapses occurs during aging provided conflicting results, possibly due to the unavailability, at the time, of unbiased methods for synapse quantitation. This study was designed to reexamine the issue by means of modern technical procedures that provide unbiased estimates of synaptic numbers. Groups of 14 young adult (5 months old) and 14 aged (28 months old) male Fischer-344 rats were compared. Synapses were examined in the middle (MML) and inner (IML) molecular layer of the hippocampal dentate gyrus, where synaptic contacts are predominantly formed by different systems of afferents, the entorhinal and commissural-associational fibers, respectively. The number of synapses per neuron was estimated with the aid of the stereological dissector technique. The results showed that the total number of synaptic contacts per neuron was significantly diminished in the MML (by 23.6%) and IML (by 22.7%) of aged rats relative to young adults. This age-related synaptic loss involved axospinous, but not axodendritic, junctions of the MML (-24.4%) and IML (-24.0%). Both perforated and nonperforated axospinous synapses (distinguished by a discontinuous or continuous postsynaptic density, respectively) exhibited an age-dependent decrease in numbers, though this decrease did not reach statistical significance in the case of perforated junctions of the IML. The observed age-related loss of axospinous synapses may underlie the reduction in the amplitude of excitatory postsynaptic potentials and the decline in functional synaptic plasticity detected in the dentate gyrus of senescent rats.

Afferent Pathways↗
PubMed1992

Structural synaptic plasticity associated with the induction of long-term potentiation is preserved in the dentate gyrus of aged rats.

Changes in synaptic numbers were examined in the hippocampal dentate gyrus of aged (28 months old) rats following the induction of long-term potentiation (LTP) by high-frequency stimulation of the medial perforant path carried out on each of 4 consecutive days. Potentiated animals were sacrificed 1 hour after the fourth stimulation. Stimulated but not potentiated and implanted but not stimulated rats of the same chronological age served as controls. Synapses were analyzed in the middle (MML) and inner (IML) molecular layer of the dentate gyrus. Using the stereological dissector technique, unbiased estimates of the number per neuron were obtained for the following morphological varieties of synapses: axodendritic synaptic junctions involving dendritic shafts, nonperforated axospinous synapses having a continuous postsynaptic density (PSD), and perforated ones distinguished by a fenestrated, horseshoe-shaped, or segmented PSD. The induction of LTP resulted in a selective increase in the number of synapses with segmented PSDs. This change was detected only in the potentiated synaptic field (MML), but not in an immediately adjacent one (IML), which was not directly stimulated during the induction of LTP. Comparison of these data with the results of our previous LTP study in young adult rats (Geinisman, Y. et al., 1991, Brain Res. 566:77-88) showed that the only significant difference in the absolute number of synaptic contacts per neuron between potentiated animals of the two chronological ages was an age-related reduction in segmented synapses of the MML. Relative increases in the number of segmented synapses per neuron were, however, virtually of the same magnitude in potentiated rats of both ages as compared with their respective controls. This finding may explain why senescent rats can be potentiated to the same extent as young ones.

Acoustic Stimulation↗
PubMed1991

Induction of long-term potentiation is associated with an increase in the number of axospinous synapses with segmented postsynaptic densities.

Long-term potentiation (LTP) is characterized by a long-lasting enhancement of synaptic efficacy which may be due to an increase in synaptic numbers. The present study was designed to verify the validity of this suggestion using recently developed unbiased methods for synapse quantitation. LTP was elicited in young adult rats by high-frequency stimulation of the medial perforant path carried out on each of 4 consecutive days. Potentiated animals were sacrificed 1 h after the fourth stimulation. Stimulated but not potentiated and implanted but not stimulated rats served as controls. Synapses were examined in the middle (MML) and inner (IML) molecular layer of the hippocampal dentate gyrus. Using the stereological disector technique, unbiased estimates of the number of synapses per neuron were differentially obtained for the following morphological synaptic types: axodendritic synapses involving dendritic shafts, non-perforated axospinous synapses exhibiting a continuous postsynaptic density (PSD) and perforated axospinous synapses distinguished by a fenestrated, horseshoe-shaped or segmented PSD. A major finding of this study is that the induction of LTP is accompanied by a selective increase in the number of synapses with segmented PSDs. This change was detected only in the potentiated synaptic field (MML), but not in an immediately adjacent one (IML) which was not directly stimulated during the induction of LTP. It is strongly suggested by the latter finding that the increase in the number of axospinous synapses exhibiting segmented PSDs is associated with LTP. Such a highly selective modification of connectivity, which involves only one particular subtype of synapses in the potentiated synaptic field, is likely to represent a structural substrate of the enduring augmentation of synaptic efficacy typical of LTP.

Animals↗
PubMed1991

A 'stress' test for memory dysfunction. Electrophysiologic manifestations of early Alzheimer's disease.

Long-latency event-related potentials (P300) were assessed in patients with early probable Alzheimer's disease (AD), age-matched controls, and young adults during a task that imposed various degrees of demand on memory. Although patients with AD did not differ from age-matched controls when one item had to be remembered, their P300 potential was dramatically reduced in amplitude or absent with increasing memory load. Aged controls did not differ from young adults on this measure. P300 latency, however, did not differentiate patients with AD. Thus, electrophysiological abnormalities detected in the context of mnemonic demand may provide a sensitive marker of the early stages of probable AD.

Adult↗
PubMed1990

The brain's record of experience: kindling-induced enlargement of the active zone in hippocampal perforated synapses.

Kindling is a consequence of intermittent electrical stimulation of a local forebrain area leading to a durable augmentation of synaptic responsiveness in the stimulated circuit. The basis for this functional change is unknown, but there is evidence suggesting that it entails a structural modification of synapses. The present report demonstrates that hippocampal kindling induces a selective enlargement of active zones in perforated axospinous synapses formed by stimulated axons. Since the active zone is the site of intracellular transmission, its enlargement involving only a certain subpopulation of synapses provides a likely structural substrate of synaptic plasticity associated with kindling.

Animals↗
PubMed1990

Increase in the relative proportion of perforated axospinous synapses following hippocampal kindling is specific for the synaptic field of stimulated axons.

A comparative analysis of axospinous synapses was performed in the middle (MML) and inner (IML) molecular layer of the hippocampal dentate gyrus of rats kindled via medial perforant path stimulation and sacrificed 4 weeks after reaching a criterion of 5 generalized seizures. The MML was a directly stimulated structure, while the IML was not. Both are immediately adjacent synaptic fields likely to be equally susceptible to any generalized effects of convulsions and hypoxia. In these two subdivisions of the molecular layer, the so-called perforated and non-perforated synapses, distinguished respectively by a discontinuous or continuous postsynaptic density, were differentially quantified. In the MML, the ratio of perforated to non-perforated synapses was found to be markedly increased in kindled rats relative to controls. In the IML, however, no change in this ratio was detected following kindling. Thus, the shift in the relative preponderance of perforated synapses over non-perforated ones is not a consequence of generalized phenomena accompanying the kindling process.

Animals↗
PubMed1989

Perforated synapses on double-headed dendritic spines: a possible structural substrate of synaptic plasticity.

Examination of axospinous synapses in serial sections obtained from the middle molecular layer of the rat dentate gyrus has revealed that some of them involve double-headed dendritic spines. Each spine head is apposed by a separate axon terminal with which it always forms a perforated synaptic contact distinguished by a discontinuous postsynaptic density. The number of perforated synapses on double-headed spines was estimated as a synapse-to-neuron ratio with the aid of the disector technique and found to be significantly increased in rats kindled via medial perforant path stimulation. These results support the notion that perforated synapses involving double-headed dendritic spines represent a structural modification related to enhanced synaptic efficacy.

Animals↗
PubMed1988

Remodeling of synaptic architecture during hippocampal "kindling".

The "kindling" phenomenon is associated with long-lasting facilitation of synaptic transmission. A possible mechanism of such facilitation could involve changes in the number of synaptic contacts. However, previous attempts to demonstrate a synaptic morphological alteration that could account for the long-term effects of kindling had failed, possibly due to the unavailability, at the time, of unbiased methods for synapse quantitation. Using the unbiased stereological disector technique, we estimated the number of synapses per neuron in the middle molecular layer of the hippocampal dentate gyrus in rats kindled by electrical stimulation of the medial perforant path with implanted electrodes. Unkindled but stimulated (coulombic control) and unstimulated but implanted rats served as controls. Animals were coded and killed 4 weeks after reaching the kindling criterion of five generalized seizures. The most important results were obtained when axospinous synapses with continuous or discontinuous postsynaptic densities ("nonperforated" or "perforated" synapses) were differentially analyzed. Kindling resulted in a selective loss of nonperforated synaptic contacts in contrast to preservation of perforated ones. Furthermore, the ratio of perforated to nonperforated synapses was increased by 45% or 40% in kindled rats relative to unstimulated or coulombic controls, respectively. These findings suggest that synaptic efficacy may depend on a balance of the two synaptic types; selective elimination of nonperforated synapses may augment the potency of remaining synaptic contacts, a process reminiscent of synaptic remodeling during development.

Algorithms↗