Biomedical subjects

T L Babb

Publications and source records attributed to T L Babb.

At least 73 records · Page 4Linked to original sources

PubMed1988

Distribution of glutamate-decarboxylase-immunoreactive neurons and synapses in the rat and monkey hippocampus: light and electron microscopy.

We have studied the distribution of gamma-aminobutyric acid (GABA) neurons, axons, and synapses in the rat and monkey hippocampal formation by using glutamate decarboxylase (GAD) immunocytochemistry together with Nissl stains, electron microscopy, and double-labeled retrograde transport of horseradish peroxidase. The numbers of GAD-containing (putative GABA) neurons and their percentages compared to all Nissl-stained neurons were calculated throughout all the various fields and strata of the mammalian hippocampus. Although their numbers are greatest in the polymorph region of the fascia dentata (FD) and in the principal cell layers stratum pyramidale (SP) and stratum granulosum (SG), GAD immunoreactive (GAD-IR) cells are numerous in other strata that contain mostly dendrites and scattered cells. These GAD-IR (putative GABA) neurons in dendritic regions may be involved in feedforward dendritic inhibition or may directly inhibit nearby neurons. We used a postmortem delay technique, which resulted in apparent diffusion of GAD into dendrites and axons and allowed better visualization of the extensive dendritic domain of GAD-IR neurons. Computerized image analysis of GAD-IR puncta indicated that putative GABA terminals were numerous on apical and basilar dendrites of all pyramidal cells but unexpectedly highest in the monkey presubiculum. In the rat, GAD-IR neurons projected axons ipsilaterally from every region to the fascia dentata and CA1; however, commissural GAD-IR axons to the fascia dentata arose from GAD-IR neurons in only the contralateral fascia dentata and subiculum. Electron microscopy of GAD-stained hippocampus identified GAD-IR neurons with non-GAD-IR (possibly excitatory) synapses and GAD-IR terminals on somata and dendrites, 80% being the symmetric type and 20% the asymmetric type. In contrast, non-GAD-IR terminals were asymmetric 80% of the time.

Animals↗

PubMed1987

Firing patterns of human limbic neurons during stereoencephalography (SEEG) and clinical temporal lobe seizures.

Comparisons of the patterns of neuronal firing and stereoencephalography (SEEG) recorded from the same microelectrodes chronically implanted in the human limbic system were made in order to study neuronal electrogenesis at onset and during propagation of focal partial complex seizures. Alert or sleeping patients were monitored during spontaneous subclinical seizures (no alterations in consciousness detectable), during auras reported by the patients as typical, and during clinical seizures with loss of consciousness, movements and post-ictal confusion. During subclinical SEEG seizures (ipsilateral, normal consciousness), few neurons increased firing (estimated at only 7%) either at the focus or at propagated sites. During auras, with altered consciousness, there were relatively few neurons that increased firing, with the estimate about 14% or twice as many as during a subclinical seizure. During the onset of a clinical seizure that involved loss of consciousness, movements and post-ictal confusion, many neurons were recruited into increased firing, with an estimate of approximately 36%. During this increased electrogenesis, neurons fired briefly in association with high-frequency local SEEG; however, the bursts were shorter than the SEEG seizure pattern. Apparently, other local neurons were recruited to fire in bursts to sustain sufficient axonal driving for widespread propagation of the seizure. When the focal SEEG slowed, the units stopped firing, which suggested that the 'focal' seizure need not be sustained for more than several seconds because propagated seizure activity was self-sustaining at distant structures. The data lead to the conclusion that SEEG seizures can be generated focally by synchronous firing of fewer than 10% of neurons in the 'epileptic pool.' However, when greater percentages of neurons are recruited in the 'epileptic focus' there is greater propagation to widespread sites, especially contralaterally, which will produce clinical partial complex seizures.

Action Potentials↗

PubMed1987

Diversity in periodic pattern of firing in human hippocampal neurons.

Firing periodicity was examined in human hippocampal neurons using autocorrelation analysis. Extracellular single-unit activities were recorded from the anterior hippocampus through fine platinum microelectrodes, and the typical firing pattern in an entire recording period was reconstructed statistically in autocorrelograms (average number of firings analyzed: 5639.0 +/- 968.1 SE, range: 1158 to 31,203; number of single-unit trains was 57). Three types of periodic firing were identified as highly consistent. The first pattern consisted of a random recurrence of high-frequency action potentials (100 to 300 Hz) and was observed as an intermittent burst. In this burst, the first 10 to 30 ms after the onset of the burst was the patterned firing of several action potentials, suggesting that the generation of this stereotyped portion of the burst is primarily due to intrinsic membrane characteristics. The second pattern was the continuous rhythmical firing with a lower frequency ranging from 1 to 30 Hz. The third pattern was a clustered rhythmical firing in which a series of short rhythmical firings recurred with regular intervals; the frequency of short rhythmical firing varied from 6.7 to 17 Hz between neurons, and the interval of the regular recurrence of these rhythmical firings ranged from 0.5 to 10 s among neurons. These firing periodicities not only cover a cellular rhythm in the theta frequency reported in the lower mammalian hippocampus but also appear to be more diverse than those previously reported for hippocampal neurons in the animal literature.

Electric Stimulation↗

PubMed1987

Structurally stable burst and synchronized firing in human amygdala neurons: auto- and cross-correlation analyses in temporal lobe epilepsy.

Burst structure and synchronized firing of bursts were studied, in the interictal period, using auto- and cross-correlation analyses in human amygdala neurons in temporal lobe epilepsy patients diagnosed as having a unilateral limbic seizure focus in anterior hippocampus and/or amygdala. Satisfactory single unit recordings were obtained from chronically implanted microelectrodes in 51 amygdala neurons, and auto-correlation analysis identified 27 of 51 neurons where burst firings recurred with regular interspike interval structures (structurally stable burst: S-burst). This structural stability was characteristic only for a short burst, or at the beginning of a series of repetitive firings, involving 2-5 action potentials. In 'non-epileptic' amygdala neurons located contralateral to the seizure focus, the average duration of S-burst was 15 msec and the number of action potentials (spikes) in the S-burst was inversely related to the interspike intervals in the S-burst, suggesting that endogenous membrane characteristics of non-epileptic amygdala neurons determine the patterns of S-burst. In contrast, in the seizure focus amygdala ('epileptic'), the duration of the S-burst was prolonged among epileptic neurons, not because of the occurrence of more action potentials within the S-burst, but because of a prolonged interspike interval within the S-burst. Furthermore, there was no relationship between the interspike interval and the number of action potentials in the S-burst, suggesting that synaptic inputs and/or extracellular environmental factors may affect an intrinsic mechanism for generating stable S-burst in epileptic neurons. Cross-correlation analysis identified synchronized firings in epileptic neurons: when two epileptic neurons both exhibited S-bursts, when either epileptic neuron exhibited S-burst, but never when neither exhibited S-bursts. Conversely, non-epileptic neurons rarely fired synchronously; even though they showed S-bursts. The difference in the pattern of S-bursts between epileptic and non-epileptic amygdala neurons seems to be the degree of firing synchrony. Our results provide, for the first time, direct evidence that human epileptogenic amygdala neurons recorded in vivo have unique burst firing patterns and significant synchronous excitatory interactions, different from a burst pattern found in non-epileptogenic amygdala neurons during the interictal period.

Action Potentials↗

PubMed1986

Neurophysiology of limbic system pathways in the rat: projections from the subicular complex and hippocampus to the entorhinal cortex.

We studied the responses of rat entorhinal neurons to electrical stimulation of the dentate gyrus, hippocampus and subicular complex. Three main results were obtained. Excitatory postsynaptic potentials were recorded in entorhinal neurons in response to electrical stimulation. Cell in layers II, III and V of the entorhinal cortex were responsive. Frequency potentiation of excitatory responses was observed when 10/s stimulation was used. Excitatory responses were followed by inhibitory postsynaptic potentials. The results provide evidence for an excitatory projection from the hippocampus and subiculum to the entorhinal cortex, and are consistent with the existence of feed-forward inhibition of entorhinal principal neurons.

Animals↗

PubMed1986

Magnetic resonance imaging in intractable partial epilepsy: correlative studies.

A study was performed evaluating magnetic resonance imaging (MRI) in 35 patients with intractable complex partial seizures in whom computed tomographic (CT) scans showed no focal abnormalities. These results were correlated with positron emission tomography evaluation (PET), the electroencephalographic ictal onset, and findings during pathological examination. Seven patients had structural lesions that were epileptogenic, detected by MRI; the lesions were tuberous sclerosis, astrocytomas, or hamartomas. Three of these 7 patients underwent PET scanning, which was normal in all. Of 18 patients with mesial temporal sclerosis, 10 were shown by PET to have temporal lobe hypometabolism, though all 18 had normal MRI findings. The results indicate that MRI contributes information to that provided by CT and PET, by detecting nonsclerotic epileptogenic lesions of the temporal lobe.

Astrocytoma↗

PubMed1986

Metabolic, morphologic and electrophysiologic profiles of human temporal lobe foci: an attempt at correlation.

Our current understanding of focal seizures strongly suggests a model of damage and associated synaptic reorganization that leads to periodic 'spontaneous' hyperexcitation and/or sustained firing that generates seizures. Our working model of a human epileptic focus assumes that there will often be inexcitability near the damage (hippocampus proper); however, the anomalous circuitry will occasionally lead to hyperexcitability whenever these anomalous (epileptic) circuits are activated synchronously in sufficient numbers to propagate discharges to normal tissue (e.g., the presubiculum) which would be normally excitable. The key role of rebound excitation following prolonged inhibition in the hippocampus is strongly supported by both physiologic and GAD immunologic results. Our ability to directly test the level of excitability of hippocampal and presubicular neurons in vivo, followed by microanatomical studies of the same resected tissue, will allow us to test our model and revise it as our results become more complete. Also, our findings will be important for relating synaptic mechanisms of seizure genesis to those demonstrated in various experimental models of focal hippocampal seizures.

Epilepsy, Temporal Lobe↗

PubMed1986

Neuronal, dendritic, and vascular profiles of human temporal lobe epilepsy correlated with cellular physiology in vivo.

Partial complex seizures are known to arise from abnormal firing of neurons in cortex that has histologic abnormalities associated with tumors, infarcts, or neuron loss. The latter pathology of sclerosis is most frequently found in the hippocampus, and partial seizures from this region are focalized by direct electrical recordings and treated by anterior temporal lobectomy. Although we can link this hippocampal sclerosis to nearby hyperexcitability, the synaptic mechanisms involved in hippocampal seizure genesis are not yet known. We have used in vivo microelectrode recordings from hippocampal neurons and found rare instances of anomalous bursting patterns as well as coupled firing. Postinhibitory "rebound excitation" has also been recorded, supporting the concept that synchronized hippocampal outputs are important for seizure genesis. Immunocytochemistry of GAD-positive inhibitory interneurons indicates no significant loss in inhibition in the sclerotic hippocampus and a normal number of inhibitory interneurons in its output target, the presubiculum. The presubiculum, with its multi-layered cortex, may amplify and propagate seizures to other cortices. Golgi and electron microscopy of epileptic neurons have shown pre- and postsynaptic alterations that may contribute to seizure genesis. Finally, ultrastructural analysis of capillaries in sclerotic hippocampus indicates deficient plasma-tissue transport that may contribute to cell loss or may alter neuronal excitability.

Capillaries↗

PubMed1985

Monitoring at the University of California, Los Angeles.

Long-term EEG monitoring with radio or cable telemetry and video recording can be performed efficiently as an organized team effort involving physicians, nurses, technologists and other ancillary personnel. We use telemetry primarily for screening patients for possible surgical treatment of partial epilepsy. The technique is also used occasionally to define better the patient's type(s) of seizures or to differentiate seizures from pseudoseizures. Important technical points include precise correlation of EEG with clinical events, choice of recording montage, use of a 1 Hz low filter, and use of sphenoidal electrodes. Patients may need to be stressed, exercised or have medications reduced to bring about a sufficient number of seizures during monitoring. Care is needed to avoid or to identify atypical seizures due to medication withdrawal.

California↗

PubMed1984

Excitatory projection of the rat subicular complex to the cingulate cortex and synaptic integration with thalamic afferents.

We studied the responses of rat cingulate cortex neurons to electrical stimulation of the subicular complex. Intracellular and 'quasi-intracellular' recordings from layer V posterior cingulate neurons showed that stimulation of the presubiculum or postsubiculum evoked EPSPs and action potentials. These were usually followed by shallow IPSPs averaging 122 ms in duration. Frequency potentiation of an EPSP was demonstrated in one case. Laminar analysis of field potentials provided evidence for a source of excitatory synaptic drive in layer II-III of the posterior cingulate cortex, where the subicular projections terminate, presumably on apical dendrites of layer V pyramids. Intracellular HRP injection of neurons showing EPSPs after subicular complex stimulation established that these responsive neurons were layer V pyramids. One cell with physiological properties characteristic of inhibitory interneurons was recorded in layer V. Stimulation of the thalamic nuclei lateralis and anterior ventralis also evoked EPSPs and action potentials in layer V cingulate neurons. In one cell it was possible to show that EPSPs evoked by presubicular stimulation and by nucleus anterior ventralis summed. These results indicate that subicular and thalamic afferents make excitatory synaptic contact onto dendrites of the same layer V cingulate neurons; that spatial summation can integrate the input from these two sources; and that inhibition from local interneurons limits the duration of this excitatory influence.

Afferent Pathways↗

PubMed1984

Habituation of human limbic neuronal response to sensory stimulation.

Hippocampal, parahippocampal gyrus, and amygdalar neuronal responses to visual and acoustic stimuli were analyzed during trains of several hundred stimulus repetitions as part of an investigation of sensory pathways to medial temporal lobe structures in complex-partial epilepsy patients who were being monitored with depth electrodes. Ten percent of more than 500 single and multiple units tested were responsive to simple sensory stimuli. The majority of the responsive units were recorded in the posterior parahippocampal gyrus (HG) during visual stimulation. Although neurons in pes hippocampi (PH; Ammons's horn) were also responsive to photic stimuli, no visually responsive units were found in amygdala. Very few units were responsive to acoustic stimuli, and these were found only in PH and amygdala, and not in HG. Significant trends of increase or decrease in response amplitude during trains of stimuli were found in all acoustically responsive units. Significant trends of visual response amplitude increase or decrease were found in 20% of PH units, and in 44% of HG units. Mean latencies of acoustically responsive units were longer than those of visually responsive units, and latencies of PH sensory units showing decremental response were longer than nondecremental PH units. Rate of response decrement was usually linear for acoustic responses and exponential for visual responses. The response dynamics of medial temporal lobe neurons are compared with those described in the animal limbic system and are related to habituation of human sensory evoked scalp potentials.

Acoustic Stimulation↗

PubMed1984

Afferent fibers to rat cingulate cortex.

Afferent fibers to the rat cingulate cortex were studied by the retrograde labeling technique using horseradish peroxidase-wheat germ agglutinin conjugate as the tracer. The results showed that the posterior cingulate cortex, but not the anterior, received input from the anterior dorsal and anterior ventral nuclei of the anterior thalamic group of nuclei (part of the so-called limbic thalamus), and from the subicular complex. The anterior cingulate cortex, but not the posterior, received input from the mediodorsal and ventral thalamic nuclei. Both posterior and anterior cingulate cortex received input from the hippocampus pars anterior; claustrum; globus pallidus; nucleus of the diagonal band of Broca (a particularly reliable source of afferent fibers); anterior medial, lateral, rhomboid, and reuniens nuclei of the thalamus; region of the medial forebrain bundle; periventricular nucleus of the hypothalamus; the dorsal and median raphe; and the locus ceruleus. Corticocortical projections were seen anterior, posterior, and lateral to the injection site, and in the homologous contralateral cingulate cortex. The results demonstrate a prominent source of cingulate afferent fibers from the subicular complex, provide evidence for a functional division of anterior and posterior cingulate cortices in the rat, and provide information about the relative anatomic importance of cingulate afferent fibers from those different regions.

Afferent Pathways↗

PubMed1984

Phagocytic and metabolic reactions to chronically implanted metal brain electrodes.

In order to study the biocompatibility of metal electrodes and insulations in the rat brain, eight different metal electrode types and two different insulations were implanted for 11, 35, 36, 37, or 63 days. Stainless steel and Nichrome were nontoxic metals, silver was toxic, and copper extremely toxic with phagocytosis active to 37 days of implantation. Active phagocytosis was easily detected by high glucose demand using 2-deoxy[14C]glucose (2-DG) autoradiography contrasted with normal 2-DG autoradiographs where phagocytes were present but not ingesting. Epoxylite, an epoxy-polyester varnish, was slightly more reactive in brain than polyimide but not statistically significant. In general, larger electrodes created more tissue reaction per se for as long as 37 days. These results suggested that a thin stainless-steel bipolar electrode will provide safe recording electrodes in either animal or human brain. The importance of these findings is that certain metals (silver, copper) cannot be used in the brain without producing necrosis and phagocytosis, whereas other metals (stainless steel, Nichrome) with varnish insulators (Epoxylite, polyimide) can be implanted without producing any detectable damage beyond that of the initial trauma and brief phagocytosis limited to the edge of the electrode track. Finally, the glucose metabolism autoradiographs differentiated active phagocytosis (copper) from inactive phagocytes (silver) when using long implants (37 days) of toxic metals.

Animals↗

PubMed1984

Phagocytic and metabolic reactions to intracerebral electrical stimulation of rat brain.

Electrical stimulation of the brain has been used with a variety of different electrode types and different stimulating intensities. Few studies have explored neural damage resulting from electrical stimulation that may render the experiment unreliable. The present study used conventional intracerebral bipolar metal stimulating electrodes, delivered a range of defined charge levels, and systematically measured "acute" metabolic effects on glucose (2-deoxy[14C]glucose) metabolism as well as "chronic" (96 h poststimulation) neuronal death and phagocytosis at the electrode surfaces. Neither charge density per phase (QD) nor total charge density per phase (TQD) were independent predictors of "safe" or damaging stimulation; however, together they provided ranges of clearly safe or damaging stimulating conditions that lasted 1 to 2 h. The lowest QD (11.11 microC/cm2/ph) was safe even at 9.1 TQD but not when the pulses totaled 9.6 TQD in 4 h. The middle QD (22.22) was safe even at 9.3 TQD but not when the 2-h pulsing totaled 11.0 TQD. The highest QD (44.44) was safe at 0.4 and 0.8 TQD but irreversibly damaging at 1.6 and 9.6 TQD. These comparisons demonstrated conditions suitable for 1 to 2 h of safe stimulation, but did not provide evidence on the cumulative effects of longer periods or higher frequencies.

Animals↗

PubMed1984

Distribution of pyramidal cell density and hyperexcitability in the epileptic human hippocampal formation.

Pyramidal cell densities in various regions of the anterior and posterior hippocampal formation were measured from en bloc temporal lobe resections and compared with presurgical stereoelectroencephalography (SEEG) data derived from depth electrodes in 12 patients with temporal lobe epilepsy. These data were compared with cell densities observed in four nonepileptic control patients. Patients who consistently exhibited anterior focal changes in the SEEG accompanying onset of ictus had cell densities that were selectively reduced in the anterior hippocampal formation but normal with respect to controls in the posterior hippocampal formation. Patients who exhibited more regional changes in the SEEG at onset of ictus had reduced cell densities in both the anterior and posterior hippocampal formation. Patients who exhibited focal spike activity in the anterior hippocampal formation as their predominant interictal SEEG pattern also had selectively reduced cell densities in the anterior hippocampal formation, while patients with widespread spiking throughout the hippocampal formation had reduced cell densities both anteriorly and posteriorly. These data support the concept that epileptogenesis occurs in or near those areas of epileptic hippocampus that are most damaged. Hippocampal sclerosis must be viewed as related to adjacent hyperexcitable or epileptogenic neurons and not solely as a passive result of repeated anoxia or ischemia.

Cerebral Cortex↗

PubMed1984

Temporal lobe volumetric cell densities in temporal lobe epilepsy.

Volumetric cell densities in 13 different subfields of the temporal lobe were calculated to test various hypotheses about mesial and lateral temporal lobe sclerosis in patients with complex partial epilepsy. In patients benefitting (primary group) from anterior temporal lobectomy (ATL), sclerosis was greater (fewer cells) in anterior than in posterior hippocampus. By contrast, the patients lacking full benefit (nonprimary group) from ATL had decreased numbers of neurons equally distributed from anterior to posterior hippocampus, indicating that zones of mesial temporal cell loss are linked to zones of epileptogenicity. These data support a model of focal hippocampal epilepsy originating from zones of cell loss and synaptic reorganization that is epileptic. There were no differences in cell densities in gyrus hippocampi or in lateral temporal gyri when patients with temporal lobe epilepsy and controls were compared. Hippocampal cell densities in mesial temporal lobe were not reduced in psychomotor epileptic patients with extrahippocampal foci consisting of foreign tissue. Variables in seizure histories were not correlated with Ammon's horn cell densities, indicating that most of the sclerosis preceded the seizures, which did virtually no significant further damage to hippocampus with repeated partial or generalized seizures.

Brain Diseases↗

PubMed1984

Increased glucose metabolism during long-duration recurrent inhibition of hippocampal pyramidal cells.

The locally subnormal brain metabolism observed in some experiments utilizing the Sokoloff 2-deoxyglucose (2-DG) method has often been attributed to postsynaptic inhibition despite the fact that inhibitory postsynaptic potentials are themselves caused by energy-requiring mechanisms. To explore this issue, neurophysiologically confirmed long-duration recurrent inhibition of hippocampal pyramidal unit firing was induced by low frequency (2 to 4 Hz) stimulation of the fornix for 60 min following intravenous infusion of [14C]-2-DG. The resulting autoradiograms showed that long-duration suppression of pyramidal cell firing was accompanied by distinctly increased hippocampal 2-DG uptake, particularly in the stratum pyramidale, which contains a dense plexus of inhibitory interneuronal terminals upon pyramidal cells. Both the pyramidal inhibition and the increased 2-DG uptake were confined to the ipsilateral hippocampus in animals with previously severed fornices and hippocampal commissures. In a second series of rats, the excitatory entorhinohippocampal "perforant path" (PP) was stimulated at low frequency (2 to 9 Hz) following 2-DG administration. At 2 to 4 Hz, each PP stimulation resulted in a brief burst of pyramidal unit firing followed by short-duration firing suppression; this result was associated with paradoxically decreased 2-DG uptake in the ipsilateral stratum molecular. By contrast, 7 to 9 Hz entorhinal stimulation induced PP-mediated excitation immediately followed by powerful intrinsic hippocampal inhibition, evidenced by prolonged pyramidal unit suppression after each stimulation. This suppression was accompanied by increased 2-DG uptake in the dentate stratum molecular and hippocampal stratum pyramidale. Thus it appeared that even with entorhinal stimulation, hippocampal 2-DG uptake was more closely associated with long-duration recurrent inhibition than with transient pyramidal excitation. Therefore, although it still remains possible that regions of hypometabolism observed in some previous 2-DG studies may actually reflect mild inhibition, other mechanisms such as disfacilitation are more likely mechanisms for this metabolic pattern.

Animals↗

PubMed1983

Demonstration of axonal projections of neurons in the rat hippocampus and subiculum by intracellular injection of HRP.

Hippocampal formation neurons of rat were injected intracellularly with horseradish peroxidase in order to trace intrinsic and extrinsic axonal projections. CA3 pyramids (n = 9) projected axons rostrally toward the fimbria, one or more Schafer collaterals toward CA1, and in two cases fibers that crossed the hippocampal commissure. Pyramids of CA1 (n = 5) projected axons to the alveus where they proceeded caudally toward the subiculum. A subset (n = 3) also projected an axonal branch rostrally toward the fimbria. These findings confirm not only major target regions of Ammon's horn pyramids, but also emphasize their divergent axonal projections that are not necessarily lamellar in organization. Axons from subicular pyramids (n = 12) projected rostrally, caudally, or in both directions. They could be traced to several other cortical regions, specifically Ammon's horn, entorhinal cortex and cingulate cortex. The results further confirm that subicular neurons are the recipient of input from the hippocampus proper and are a principal source of efferents from the hippocampal formation. A multi-process neuron in CA1 with physiologic properties associated with inhibitory interneurons was filled and traced in detail. It most resembled the poligonal basket cells that Lorente de Nó described, having long radially oriented dendrites extending as far as stratum lacunosum-moleculare. The presence of putative inhibitory interneuron dendrites in stratum lacunosum-moleculare suggests some role other than traditional recurrent inhibition for these dendritic segments, and two possible circuits are described.

Animals↗