Bolek Srebro

Changes in acetylcholinesterase and distribution of degenerating fibres in the hippocampal region after septal lesions in the rat

Abstract The effect of septal lesions on histochemically demonstrable acetylcholinesterase in the hippocampal region of the rat was studied. The earliest changes in hippocampal acetylcholinesterase were detected 36 h after operation. Only medial septal lesions, not lesions of the lateral septum or lateral hypothalamus, visibly affected the enzyme. The distribution of acetylcholinesterase and loss of enzyme in different layers and areas after medial septal lesions were correlated with the distribution of degenerating axons and terminals in Fink-Heimer preparations of the same material. The latter showed a rather diffuse distribution of degeneration in all parts of the hippocampal region, more extensive than described in Nauta material with septal lesions.

Behavioral effects of selective midbrain raphe lesions in the rat.

Lesions were produced in the median (n = 8), dorsal (n = 7) or both (n = 7) midbrain raphe nuclei and their effects on behavior (days 16-54 postoperatively) compared to that of controls (n = 9). In addition, forebrain 5-hydroxytryptamine (5-HT) concentration were determined. Only the median and combined lesion groups showed increased running wheel and open field activity, as well as enhanced reactivity to novel stimuli and environmental change. None of the lesion groups, however, showed changes in home cage activity on postoperative day 21. Although all lesion groups were deficient in the acquisition and retention of one-way avoidance, the deficits were of a greater magnitude in the median and combined lesion groups. The latter two groups, furthermore, were impaired in forced extinction of the one-way avoidance response, but only the combined lesion group evidenced facilitation of two-way avoidance acquistion. Thus, in contrast to the effects of median or combined raphe lesions, lesions in the dorsal raphe nucleus affected few of the behavioral parameters studied. These results suggest that the dorsal raphe nucleus plays a different behavioral role than the median raphe nucleus. The median nucleus appears to be involved in the regulation of activity level, the reaction to novelty and environmental change, and the response to aversive stimuli. Possible mechanisms for the observed behavioral changes are discussed, as well as their apparent similarity to the effects of other mesencephalic and limbic lesions. Lastly, the median, dorsal and combined raphe lesions lowered forebraine 5-HT but 26, 65, and 77%, respectively, versus controls. These reductions differed significantly from each other, and with previously reported data indicate that the dorsal raphe nucleus in the principal origin of forebrain 5-HT. It is suggested, furthermore, that the behavioral effects of midbrain raphe lesions are not due primarily to their associated reduction in forebrain 5-HT.

Activity, avoidance learning and regional 5-hydroxytryptamine following intra-brain stem 5,7-dihydroxytryptamine and electrolytic midbrain raphe lesions in the rat

Rats underwent one of the following treatments: (1) electrocoagulation of both the dorsal and median midbrain raphe nuclei; (2) 5,7-dihydroxytryptamine creatinine sulfate (5,7-DHT) injection (10 mug, as the salt, in 5 mul vehicle) into the vicinity of each midbrain raphe nucleus; (3) intra-brain stem vehicle (5 mul of 0.2% ascorbic acid in isotonic saline) injections; or, (4) a control operation. Open field activity and one-way avoidance conditioning were examined on postoperative days 16-23. Regional central 5-hydroxytryptamine (5-HT) and catecholamine (CA) concentrations were determined 25-27 days postoperatively. Regional 5-HT levels were greatly reduced following 5,7-DHT administration and electrolytic raphe lesions. The 5,7-DHT rats also showed a reduction in spinal 5-HT content. Central CA concentrations were not affected. Variation in the pattern of regional 5-HT changes after 5,7-DHT treatment was observed but appeared to be related to the adequacy of the dorsal raphe (B7) injection. Only the electrolytic raphe lesion animals, however, showed increased locomotor activity and retarded acquisition and forced-extinction of the one-way avoidance response. In contrast, no significant differences were observed in the open field and avoidance behavior of the 5,7-DHT, vehicle, and control groups. The hyperactivity and impaired one-way avoidance performance observed after electrolytic midbrain raphe lesions are not related simply to reductions in regional forebrain 5-HT and may well be due to damage of non-serotonergic neural systems. Clearly, the behavioral effects of central 5-HT depletion depend on the method employed. The role of 5-HT in regulating activity level and mediating avoidance behavior, furthermore, remains to be determined.

Activation of AP5-sensitive NMDA Receptors is Not Required to Induce LTP of Synaptic Transmission in the Lateral Perforant Path

The role of the N‐methyl‐D‐aspartate (NMDA) type of glutamate receptor in long‐term potentiation (LTP) of the medial (MPP) and lateral (LPP) divisions of the perforant path‐granule cell system was investigated in urethane‐anaesthetized rats. A stimulating electrode was positioned in the dorsomedial or ventrolateral aspect of the angular bundle for selective activation of either the MPP or LPP, respectively. A push‐pull cannula served to focally perfuse artificial cerebrospinal fluid (ACSF) across the perforant path synaptic zone, while evoked potentials were monitored in the dentate hilus. Identification of LPP and MPP responses was based on (1) differences in population excitatory postsynaptic potential (EPSP) waveform obtained during stimulus depth profiles, and (2) differential sensitivity of evoked EPSPs to the glutamate receptor agonist L‐aminophosphonobutyrate (AP4), and the antagonist γ‐D‐glutamylglycine (DGG). High‐frequency stimulation (400 Hz, 8 bursts of 8 pulses) applied to the lateral and medial perforant path elicited LTP of the EPSP and population spike in rats perfused with standard medium. In the MPP, LTP was almost completely blocked when D‐aminophosphonopentanoate (AP5; 100 μM), a selective NMDA receptor antagonist, was perfused during the tetanus. Surprisingly, in the LPP experiments, AP5 did not impair induction of the ‘synaptic’ EPSP component of LTP. This occurred despite the ability of AP5 to block LTP of the LPP evoked population spike. The results suggest the existence of a novel, NMDA receptor‐independent form of synaptic LTP in the lateral perforant path.

Induction of long-term depression and potentiation by low- and high-frequency stimulation in the dentate area of the anesthetized rat: magnitude, time course and EEG

We investigated the possible importance of stimulus train frequency for the induction and magnitude of long-term synaptic plasticity in the perforant path-granule cell pathway. Under the same experimental conditions, low- (15 Hz) or high-frequency (400 Hz) stimulation could elicit a profound long-term depression (LTD), or typical long-term potentiation (LTP), of the population spike amplitude, excitatory postsynaptic potential (EPSP) amplitude and spike onset latency. In addition, changes in the relationship between the EPSP and population spike amplitude indicated that granule cell excitability was enhanced during LTP and reduced during LTD. LTD occurred primarily after low-frequency stimulation (5 of 6 cases), and was always accompanied by striking changes in the EEG, most notably a biphasic slow potential. While the EEG changes were confined to the first 5 min after the tetanus, LTD lasted from 1 to 4 h. The nature of the EEG events is still unclear, it is suggested that they may represent a spreading depression-like episode. Finally, we found that LTP evoked by high-frequency stimulation was larger and generally reached peak magnitude faster than when it followed low-frequency stimulation. A possible mechanism and role for hippocampal LTD is proposed.

Acetylcholinesterase histochemistry of the septal region in rat and human: Distribution of enzyme activity

The decrease in acetylcholinesterase (ACHE) activity in the hippocampus of the rat following experimental destruction of the medial septum13, iv prompted us to use the Koelle s copper thiocholine method to map the AChE-reacting structures of the septum in the rat. A short survey of our findings has been published is. Recently, Biatowas and Narkiewicz 4 presented a general description of the histochemical topography of AChE in the septum of the rat which is similar to our own findings and those of Jacobowitz and Palkovits 7. The present report represents an extension of these studies, and includes a brief note on the experimental demonstration of an intrinsic AChE-containing fibre connection in the septum of the rat. In addition, this communication will provide a very preliminary report on AChE-reacting components of the human septum verum based on the study of normal material obtained during autopsy. Unfixed cryostat sections from rat and human septum were incubated according to the modified Koelle copper thiocholine method for frozen sections 6,13. Rat brains with medial septal lesions were treated in the same manner. In addition, a few had parallel sections processed according to the modified Fink-Heimer method 13. The nomenclature employed follows a modification of Andy and Stephans classification of the septal nuclei in the cat and human brain 1-3.

Effects of lateral and medial septal lesions on exploratory behavior in the albino rat

The effects of selective medial and lateral septal lesions on exploratory behavior were studied in the rat. Three types of open-field test and two tests of object exploration were used. In the first experiment, medial but not lateral septal lesions abolished exploration of an open-field accessible from the home-cage. No effects of either of the lesions were found in a standard open-field (Experiment 2). In the third experiment, rats with medial septal lesions were less active and showed a preference for the smaller compartments of the testing apparatus. These results suggest that a change in exploratory behavior following medial septal lesions may be primarily due to their effect on emotionality (increased fear). Two tests of object exploration (Experiments 4 and 5) showed that both types of selective septal lesions enhanced approaches to the novel object placed in the home-cage, but they did not affect object exploration and object preference in other conditions (Experiment 5). The same experiments revealed an increased level of activity (rearing and ambulation) in the rats with lateral septal lesions. It is concluded that the effect of medial septal lesions on exploration is due to increased fear of novel places (but not objects). Lateral septal lesions, on the other hand, increase activity in the rats but there is no evidence that this activity represents enhanced exploration.

Some enzyme histochemical characteristics of the human hippocampus.

SummaryThe histochemical distribution of acetylcholinesterase (AChE) and α-glycerophosphate dehydrogenase (α-GPDH) was studied in the area dentata and hippocampus proper of the human brain. Although differences did exist, there were many features in common with the distribution of these two enzymes in the rat and guinea pig. The laminar chemoarchitectonic picture was not as distinct in the human brain as in the rat and guinea pig. Most of the AChE reaction products were confined to the neuropil, with the strongest staining intensity in supra- and infrapyramidal zones. The layer of mossy fibres (stratum lucidum), was characteristically pale. On the other hand, AChE-positive cell bodies were observed in the hilus of the area dentata and a few scattered cells in the hippocampus proper. The AChE reaction products were sparse in the pyramidal cells, conforming similar observations in the rat and guinea pig.Based on our previous description of the AChE-positive cell bodies and fibres in the human septum and a considerable body of experimental material obtained in the rat, it is suggested that most of the AChE in the dentate area and the hippocampus proper is confined to terminals of cholinergic septal efferents in both man and other species. α-GPDH was particularly reactive in the cell layers, hilus fasciae dentatae and the layer of mossy fibers. These observations are similar to those described for the rat and guinea pig. They indicate, furthermore, a particular metabolic property common to the archicortex of man and other species.

Changes in postnatal development of acetylcholinesterase in the hippocampal region after early septal lesions in the rat

Abstract The Koelle copper thiocholine method was used to evaluate the effects of early postnatal septal lesions on histochemically demonstrable acetylcholinesterase (AChE) activity in the hippocampal region of the rat. Septal lesions made on the 5th or 8th day of life resulted in an almost total and permanent prevention of development of AChE-containing neuropil in the hippocampus and the dentate area. This effect was more pronounced in these areas than in the posterior parts of the hippocampal region (the entorhinal area, para-and presubiculum). The effect of early lesions was already discernible 2 days post-operatively, reducing the rapid onset of the neuropil stain in all areas of the hippocampal region observed in the normal animals during the second and third postnatal week. Adult animals which had received septal lesions in early postnatal life, showed stronger AChE activity in the presubiculum than did adults with fresh lesions (e.g. 6 days survival). This may indicate that in the former animals AChE-positive afferents had sprouted in the presubiculum.

Acetylcholinesterase Histochemistry of the Septal Region in the Rat

Based on the normal and post-lesion distribution of AChE-contining cell bodies and fibres, Lewis and Shute (13) have described the existence of several “cholinergic systems” in the rat brain. One of the most prominent forebrain systems was defined as “groups of AChE-containing neurons which are intimately related to the hippocampal formation and its projection pathways in the fore-brain and mid-brain” (13). The main part of this system consists of a cholinergic septo-hippocampal projection, the so-called “septal radiation”, which originates in the AChE-rich cell bodies of the medial septal and diagonal band nuclei. Subsequently, the cholinergic nature of these cells in the medial septum received a variety of indirect evidence from the experimental histochemical and quantitative neurochemical analyses (3,5,12,14,19,20).