Dorsal hippocampal kindling produces long-lasting changes in the origin of spontaneous discharges in the piriform versus perirhinal cortex in vitro.

In an in vitro slice preparation of the amygdala-piriform-perirhinal cortex (A-P area), it was shown previously (McIntyre, D.C., Plant, J. R., 1993. Long-lasting changes in the origin of spontaneous discharges from amygdala-kindled rats: piriform vs. perirhinal cortex in vitro, Brain Res. 624, 268-276) that the infrequent spontaneous field potentials that initially originated in or near the perirhinal (PRh) cortex of slices from control rats began instead in the piriform (Pir) cortex of amygdala-kindled rats. This change in onset was only observed in the A-P area ipsilateral to the kindled amygdala. In the present experiment, we determined whether similar changes in activity were evident following kindling from a different limbic site, the dorsal hippocampus (DH). Kindling of the DH resulted in changes in the origin of the spontaneous discharges in the A-P area similar to amygdala kindling but, importantly, the changes involved both hemispheres. In addition, the origin of spontaneous discharges in slices from partial kindled rats (those that received as many hippocampal afterdischarges as the fully kindled rats but had not developed generalized convulsive responses) initially were similar to control tissue, but, during 0 Mg(2+) perfusion, changed more quickly than control tissue to mimic the profile of generalized kindled rats. The enduring changes in A-P area excitability caused by previous generalized kindling highlights the importance of the A-P area in convulsive generalization of limbic-kindled seizures.

Neurotrophin modulation of NMDA receptors in cultured murine and isolated rat neurons.

Neurotrophin modulation of NMDA receptors in cultured murine and isolated rat neurons. J. Neurophysiol. 78: 2363-2371, 1997. Patch-clamp and calcium imaging techniques were used to assess the acute effects of the neurotrophins, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and nerve growth factor (NGF), on the responses of cultured and acutely isolated hippocampal and cultured striatal neurons to the glutamate receptor agonist N-methyl--aspartic acid (NMDA). The effects of BDNF on NMDA-activated currents were examined in greater detail. Currents evoked by NMDA, and the accompanying changes in intracellular calcium, were enhanced by low concentrations of the neurotrophins (1-20 ng/ml). The potentiation by the neurotrophins was rapid in onset and offset (<1 s). The neurotrophins also reduced desensitization of these currents in most cells. The enhancement of NMDA-activated currents by BDNF was observed using both perforated and whole cell patch recording techniques and could be demonstrated in outside-out patches. Furthermore, its effects were not attenuated by pretreatment with the protein kinase inhibitors genistein or 1-(5-isoquinolynesulfony)2-methylpiperazine (H7). Therefore, the actions of BDNF do not appear to be mediated by phosphorylation. Similar enhancements were observed with NT-3 and NT-4 and with NGF despite the fact that hippocampal neurons lack TrkA receptors. All together this evidence suggests that the enhancement of NMDA-evoked currents is unlikely to be mediated through the activation of growth factor receptors. Modulation of NMDA responses by BDNF was dependent on the concentration of extracellular glycine. The most pronounced potentiation by BDNF was observed at low concentrations, whereas no potentiation was observed in saturating concentrations of glycine, suggesting that BDNF may have increased the affinity of the NMDA receptor for glycine. However, the competitive glycine-site antagonist 7-chloro-kynurenic acid blocked the enhancement by BDNF without shifting the dose-inhibition relationship for this antagonist, and Mg2+ consistently depressed the potentiation of NMDA-evoked currents by BDNF, indicating that BDNF does not alter glycine affinity. BDNF also reversibly increased the probability of opening of NMDA channels recorded from outside-out patches taken from cultured hippocampal neurons. Other unrelated peptides including dynorphin and somatostatin also caused a glycine-dependent enhancement of NMDA currents and depressed the currents in saturating concentrations of glycine. In contrast, a shortened analogue dynorphin (6-17), which lacks N-terminus glycine residues, and another peptide met-enkephalin were without effects on NMDA currents recorded in low concentrations of glycine. Our results suggest that neurotrophins and other peptides can serve as glycine-like ligands for the NMDA receptor.

Oscillatory and burst discharge across electrosensory topographic maps.

1. Three parallel maps of the distribution of tuberous electroreceptor inputs are found in the medullary electrosensory lateral line lobe (ELL) of weakly electric fish. Pyramidal cells in each map are known to respond differentially to the frequency of amplitude modulations (AMs) of external electric fields in vivo. We used an in vitro ELL slice preparation of Apteronotus leptorhynchus to compare the characteristics of spontaneously active single units across the three tuberous maps. It was our objective to determine whether spontaneous bursting activity of pyramidal cells in each map correlates with the known AM frequency selectivities of pyramidal cells in vivo. 2. Single-unit discharges were recorded from the pyramidal cell layer of the centromedial segment (CMS), centrolateral segment (CLS), and lateral segment (LS) of the ELL. Stochastic analysis of interspike intervals (ISIs) was used to identify bursting and nonbursting unit activity, and to separately analyze intra- and interburst ISIs. Four ISI patterns were identified as 1) bursting, 2) regular spiking, 3) irregular spiking, and 4) highly irregular spiking. This work focuses primarily on the characteristics of bursting units across the ELL segments. 3. Spontaneous bursting discharge was identified in all three maps (68 of 97 units), with several characteristics changing in a gradual manner across the maps. The coefficient of variation (CV) of ISIs and intraburst ISIs decreased significantly from the CMS to the LS, whereas the CV of burst periods increased significantly from the CMS to the LS. Autocorrelations and power spectral density analysis identified units discharging in an oscillatory manner with the following ratio: CMS, 75%; CLS, 4%; LS, 8%. 4. The mean period of spike bursts decreased significantly across the segments (CMS, 2.7 s; CLS, 1.2 s; LS, 1.1 s) primarily because of a shortening of mean burst duration (CMS, 1.0 s; CLS, 0.1 s; LS, 0.05 s). The average number of spikes per burst decreased significantly across the maps (CMS, 61; CLS, 8; LS, 8), whereas the average frequency of spikes per burst increased (CMS, 90 Hz; CLS, 130 Hz; LS, 178 Hz), mainly through an increase in the maximal frequencies attained by units within each map. 5. Bursts in the CMS were unstructured in that the intraburst ISIs were serially independent, whereas for many units in the CLS and especially the LS there were serial dependencies of successive spikes, with alternating short and long ISIs during the burst. 6. These data reveal that the characteristics of bursting unit activity differ between the CMS, CLS, and LS maps in vitro, implying a modulation of the factors underlying burst discharge across multiple sensory maps. Because the pattern of change in burst activity between these maps parallels that of pyramidal cell AM frequency selectivity in vivo, oscillatory and burst discharge may represent the cellular mechanism used to tune these cells to specific frequencies of afferent input during electrolocation and electrocommunication.

Limitations of the prehospital index in identifying patients in need of a major trauma center.

STUDY OBJECTIVE: To evaluate the usefulness of the prehospital index (PHI) as a triage tool in a population of trauma patients. DESIGN: Retrospective analysis. SETTING: The two adult trauma centers in Calgary, Alberta, Canada, serving a population of 1.2 million. PARTICIPANTS: Six hundred forty-four consecutive patients admitted during an 18-month period with injury severity scores (ISSs) of 16 or more. RESULTS: PHI of 4 or more was statistically related to death within 72 hours of emergency department presentation (P < .00001), emergency surgery within 24 hours (P < .039), emergency surgery within 4 hours (P < .00001), and emergency surgery within 4 hours or death within 72 hours (P < .0001). A more important statistic, however, in the evaluation of a screening tool is sensitivity. PHI of 4 or more had a sensitivity of 98% in identifying mortality but had sensitivity of only 59% for emergency surgery within 24 hours and 71% for emergency surgery within 4 hours. CONCLUSION: PHI of 4 or more had limitations as a screening tool for triage in our study population because of the high number of patients it categorized as having minor trauma who required emergency surgery.

Response of a promethazine-induced coma to flumazenil.

We report the first case of a patient in a promethazine-induced coma responding to treatment with flumazenil. A literature search conducted to determine the mechanism behind the antagonism of this overdose showed that promethazine interacts with receptors in the central nervous system. Sedative effects may, in fact, be mediated through the benzodiazepine receptor. We concluded that flumazenil can antagonize the sedative effects of promethazine at these receptors to return the patient to a wakeful state.

Long-lasting changes in the origin of spontaneous discharges from amygdala-kindled rats: piriform vs. perirhinal cortex in vitro.

The origin of spontaneous field potentials in coronal slices of the amygdala-piriform-perirhinal area (A-P area) from amygdala-kindled and control rats was assessed. In Expt. 1, the field potentials initially originated in the perirhinal (PRh) cortex of control tissue while they originated in the piriform (Pir) cortex of amygdala-kindled tissue. In Expt. 2, this kindling-based change was observed in the A-P area ipsilateral but not contralateral to the kindled amygdala. In both experiments, subsequent exposure to perfusion medium containing 0 Mg2+ resulted in the genesis of strong discharges in both control and kindled tissues. After 2-3 h of such treatment, the origin of spontaneous discharges in control tissue changed from the PRh to the Pir area and persisted in a reduced form during reperfusion with medium containing Mg2+. This change in origin of the discharges in control tissue appeared similar to that seen in previously kindled tissue. In Expt. 3, during exposure to 0 Mg2+, the response of the basolateral amygdala (BLA) was compared with the Pir and PRh areas. Independent of the PRh discharge, the BLA discharge closely followed the Pir discharge both in time and morphology. These lasting changes in the ipsilateral A-P area in vitro must be related in vivo to the change which allows the kindled A-P area to participate in the triggering of generalized limbic-kindled convulsions.

Laceration of vertebral artery. An historic boxing death.

An historic case of a boxing death (c. 1913) was reviewed, since the cause of death given at the time is now deemed incorrect. Using current literature on traumatic basal subarachnoid hemorrhage, the cause of death is now hypothesized to have been a tear in the right vertebral artery associated with hyperextension and rotation of the neck.

Pyriform cortex involvement in kindling.

Evidence suggests that the pyriform cortex (PC) may play an important role in the genesis, if not the maintenance, of secondarily generalized limbic kindled seizures. For example, it has been shown that the fastest rates of kindling are observed from structures most directly related to the PC, and that the latter develops epileptic burst responses before all other structures, independent of the kindling site. This seizure sensitivity of the PC is reflected additionally in its inevitable loss in the face of protracted seizure, i.e., status epilepticus. In conclusion we briefly review our electrophysiological data from amygdala-pyriform cortex slices which show that the PC and overlying perirhinal cortex (PRC) possess a strong disposition for developing spontaneous rhythmic burst discharges. Further it was observed that the PRC response always led the PC event in control tissue, but rarely in kindled tissue. This suggests a functional change in the relationship between these two areas as a result of amygdala kindling. The significance of this alteration is yet undetermined.