Direct projections from Ammon's horn to the septum in the cat

Summary Direct projections from Ammon's horn to the septum were studied in the cat by the anterograde tracing method after injecting WGA-HRP (wheat germ agglutinin-horseradish peroxidase conjugate) into Ammon's horn. The results were further confirmed by the retrograde WGA-HRP method after injecting WGA-HRP into the septum. Pyramidal neurons in fields CA1, CA2 and CA3 were observed to send their axons ipsilaterally to the lateral septal nucleus; the septal parts of the hippocampus sent projection fibers to the dorsomedial portions of the lateral septal nucleus via the medial aspects of the subcallosal fornix, while the hippocampal regions successively more proximal to the temporal pole sent projection fibers to progressively more ventrolateral portions of the lateral septal nucleus via more lateral aspects of the subcallosal fornix. It was also found that the septal parts of fields CA1, CA2 and CA3 sent projection fibers bilaterally to the dorsomedial aspects of the lateral septal nucleus. Field CA4 appeared to send projection fibers only sparsely, if at all, to the medial septal nucleus. The rudimentary parts of the hippocampal formation, taenia tecta and indusium griseum, were found to have reciprocal ipsilateral connections with the dorsal portions of the lateral septal nucleus.     

Organization of identified fiber tracts in the rat fimbria-fornix: an anterograde tracing and electron microscopic study

The fimbria is a major route for afferent and efferent fibers of the hippocampal formation. However, little is known about the intrinsic organization of the fimbria-fornix complex. In this study, the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHAL) was used to analyze the ultrastructure and topography of identified fiber tracts within the fimbria-fornix. Septo-hippocampal fibers are loosely distributed throughout the fimbria-fornix. Commissural fibers cross the midline in the ventral hippocampal commissure and form a tight fiber bundle in the fimbria. Crossed entorhino-hippocampal fibers cross the midline in the ventral hippocampal commissure rostral to the commissural fiber bundle, and crossed entorhino-entorhinal fibers pass through the dorsal hippocampal commissure. This suggests a topographical organization of fiber tracts within the fimbria-fornix that reflects the laminar organization of the hippocampal target structure: fibers of the diffusely terminating septohippocampal projection are loosely distributed throughout the fimbria-fornix, while those projections that are known to terminate in specific laminae of the hippocampal formation (commissural projection, crossed entorhino-hippocampal projection) form fiber bundles within the fimbria and the ventral hippocampal commissure.Abbreviations A Astrocyte - CA1, CA3 hippocampal subfields - CC corpus callosum - D dendrite - DG dentate gyrus - DHC dorsal hippocampal commissure - Fi fimbria - LS lateral septal area - LV lateral ventricle - O oligodendrocyte - SFO subfornical organ - VHC ventral hippocampal commissure     

The organization of the fimbria, dorsal fornix and ventral hippocampal commissure in the rat

Summary The morphological organization of the two principal efferent pathways of the hippocampal formation — the fimbria and the dorsal fornix — and of the interhippocampal fibers that cross in the ventral hippocampal commissure, has been studied autoradiographically following injections of ³H-amino acids into the relevant cytoarchitectonic fields. To a considerable extent the rostrally-directed fibers from each cytoarchitectonic field remain topographically segregated within the fimbria or dorsal fornix, their locations being determined by the relative levels at which they join these bundles. Thus, the fibers from the subicular region tend to be aggregated along the ependymal border of the fimbria while those from the hilar region of the dentate gyrus are medially-placed along its pial margin. Similarly, the efferents from the septal and temporal parts of the various fields are distributed along the proximo-distal dimension of the fimbria, from its base (adjacent to field CA₃) to its tip. The dorsal fornix contains fibers from the septal (dorsal) part of the subiculum and field CA₁; although there appears to be some overlap, the subicular efferents tend to be more medially placed while those from CA₁ are further lateral. The topographic organization of the fibers in the fimbria is reflected in the arrangement of the crossed components in the hippocampal commissure. Those arising at more temporal levels cross most rostrally while those from the septal pole of field CA₃ cross in the caudal part of the commissure; those from the hilar region of the dentate gyrus cross most ventrally, while those from the more lateral parts of field CA₃ (CA_3b and CA_3a) cross at successively more dorsal levels.We estimate that the fimbria contains about 900,000 fibers of which approximately 700,000 are myelinated (with internal diameters ranging between 0.1 and 2.8m; mean 0.78 m) and just over 200,000 are unmyelinated (with diameters between 0.1 and 0.8 m; mean 0.24 m).Supported by Grants EY-01255, NS-10943 and NS-13267 from the National Institutes of Health, and by a grant from the Sloan Foundation. We should like to thank Mrs. LueVern Bell and Mrs. Pamela Seyer for their excellent histological work and Mrs. Mary Murphy for secretarial help     

Evidence for a ventral septal projection to the hippocampal formation of the rat

Summary In a series of experiments in which the known projections of the septal complex to the hippocampal formation have been transected, we have used both anterograde and retrograde tracing techniques in an attempt to demonstrate a ventral septo-hippocampal pathway. In cases where transections of the fimbria, dorsal fornix and supracallosal stria were complete, injections of the retrograde tracers wheat germ agglutinin-conjugated horseradish peroxidase or Fast blue, resulted in labeled cells in the ipsilateral septal complex, primarily in the nucleus of the diagonal band. The number of cells labeled in these experiments was approximately 5–10% of that seen in experiments in animals with intact dorsal pathways who had received similar injections. The presence of a ventral pathway was confirmed in anterograde labeling experiments in which injections of ³H-amino acids were made into the septal complex. The autoradiogfaphs demonstrated that the projection terminates most heavily in the entorhinal cortex and to a lesser extent in the ventral subicular complex; there may be an additional minor projection to the temporal half of the hippocampus and dentate gyrus. Finally, using double labeling procedures, we were able to demonstrate that at least a portion of the cell population that gives rise to the ventral pathway demonstrates choline acetyltransferase immunoreactivity and is presumably cholinergic.Abbreviations ac Anterior commissure - ACB Nucleus accumbens - AH Anterior hypothalamic nucleus - AHA Amygdalo-hippocampal area - BL Basolateral nucleus (amygdala) - BM Basomedial nucleus (amygdala) - c Cingulum bundle - CE Central nucleus (amygdala) - cc Corpus callosum - CIN Cingulate cortex - CO Cortical nucleus (amygdala) - CP Caudate-putamen - df Dorsal fornix - DG Dentate gyrus - EN Endopiriform nucleus - f Fimbria-fornix - GP Globus pallidus - Hb Habenular nuclei - ic Internal capsule - L Lateral nucleus (amygdala) - LEC Lateral entorhinal cortex - LH Lateral hypothalamic area - LS Lateral septal nucleus - ME Medial nucleus (amygdala) - MEC Medial entorhinal cortex - mfb Medial forebrain bundle - MMN Medial mamillary nucleus - MS Medial septal nucleus - NDB Nucleus of the diagonal band - OLF Olfactory cortex - ot Optic tract - PAC Periamygdaloid cortex - PV Paraventricular nucleus (thalamus) - RI Regio inferior (hippocampus) - RS Regio superior (hippocampus) - rs Rhinal sulcus - S Subiculum - scs Supracallosal striae - sm Stria medullaris - SUM Supramamillary nucleus - TU Olfactory tubercle - V Ventricle - VMH Ventromedial hypothalamic nucleus     

Ontogenetic development of septal nuclei in the rat

Summary Prenatal development of septal cell groups was studied in the rat on samples taken daily from the 14th day of gestation until birth. Coronal serial sections of brains were prepared in which the topography coordinates of septal nuclei were determined, their section profiles measured and their volumes calculated. The rat septum begins to develop on embryonic days 14–15. First the individual neurons start to differentiate, then cell groups characteristic for the adult are formed between days 14 and 17, which is followed by the delineation of nuclei. The only exception is the anterior subdivision of the lateral septal nucleus where the formation of the nucleus precedes the differentiation of its constituent cells. The individual nuclei start to develop at different times defined by a medio-lateral gradient of cell migration. By embryonic day 20 the formation of the nuclei can be considered as complete: all septal nuclei and their subdivisions are to be recognized and distinguished from each other.Abbreviations CA Anterior commissure - CC corpus callosum - CH hippocampal commissure - dm dorsal septal nucleus, magnocellular part - dp dorsal septal nucleus, parvocellular part - f fimbrial septal nucleus - FI fimbria septi - FX fornix - H hippocampal rudiment - i intermediate septal nucleus - l lateral septal nucleus - la lateral septal nucleus, anterior part - ld lateral septal nucleus, dorsal part - lv lateral septal nucleus, ventral part - md medial septal nucleus, dorsal part - mv medial septal nucleus, ventral part - NE neuroepithelium - ni bed nucleus of the commissura fornicis - po median preoptic nucleus - sfo subfornical organ - t triangular septal nucleus - td nucleus of the diagonal tract (Broca) - VL lateral ventricle     

Hormonal regulation of hippocampal spine synapse density involves subcortical mediation

It is well established that estrogen has positive effects on the density of pyramidal cell spines in the hippocampal CA1 subfield. This study explored whether afferent connections of the hippocampus that come from estrogen-sensitive subcortical structures, including the septal complex, median raphe and supramammillary area, play a role in this estrogen-induced hippocampal synaptic plasticity. These particular subcortical structures have major influences on hippocampal activity, including theta rhythm and long-term potentiation. The latter also promotes the formation of new synapses. All of the rats were ovariectomized; the fimbria/fornix, which contains the majority of subcortical efferents to the hippocampus, was transected unilaterally in each, and half of the animals received estrogen replacement. Using unbiased electron microscopic stereological methods, the CA1 pyramidal cell spine synapse density was calculated. In the estrogen-treated rats, contralateral to the fimbria/fornix transection, the spine density of CA1 pyramidal cells increased dramatically, compared to the spine density values of both the ipsilateral and contralateral hippocampi of non-estrogen-treated animals and to that of the ipsilateral hippocampus of the estrogen replaced rats.These observations indicate that fimbria/fornix transection itself does not considerably influence CA1 area pyramidal cell spine density and, most importantly, that the estrogenic effect on hippocampal morphology, in addition to directly affecting the hippocampus, involves subcortical mediation.     

大鼠背海马CA_1区若干神经联系的观察——HRP法

将HRP分别用微电泳注入10只大鼠的背海马CA_1区起层或辐射层,观察了下述通路的标记细胞位置和轴突走向:1.内侧隔核—背海马CA_1通路,轴突经背穹隆,海马槽直抵背海马CA_1区,不经海马繖女末梢既终止于起层又穿过锥体细胞层而终止于辐射层。2.海马联合通路,抵背海马CA_1区者主要由对侧CA_4锥体细胞发出的纤维组成,但终止于起层的纤维部分来自对侧CA_3区。3.海马内联系,在CA_3区透明层出现致密点状标记物。     

Adenosine inhibits the synaptic potentials in rat septal nucleus neurons mediated through pre- and postsynaptic A1-adenosine receptors

Intracellular and voltage-clamp recordings were made from neurons in rat brain slices containing dorsolateral septal nucleus (DLSN), in vitro. Bath application of adenosine (100 μM) produced a hyperpolarization (2–15 mV) in 46% of DLSN neurons (AH-neurons); in the remaining 54% neurons (non-AH-neurons), no hyperpolarization to adenosine was observed. Adenosine (1–300 μM) depressed not only the excitatory postsynaptic potential (EPSP) but also the inhibitory postsynaptic potential (IPSP) and the late hyperpolarizing potential (LHP) evoked by stimulation of the hippocampal CA3 area or the fimbria/fornix pathway in both AH- and non-AH-neurons. In non-AH-neurons, adenosine did not block current responses resulting from glutamate, muscimol or baclofen applied directly to DLSN neurons. In AH-neurons, adenosine partially depressed the baclofen-induced outward current. Adenosine did not block the directly-evoked IPSP (monosynaptic IPSP) as well as the glutamate-induced (hyperpolarizing) postsynaptic potential (PSP) that is mediated by GABA released from interneurons. These results suggest that adenosine does not directly inhibit the release of GABA. The effects of adenosine was mimicked by selective A₁-receptor agonists and was blocked by selective A₁-receptor antagonists. Pertussis toxin (PTX) blocked the hyperpolarization induced by adenosine or baclofen applied exogenously. Adenosine consistently produced presynaptic inhibition of the EPSP even in DLSN neurons treated with PTX. We conclude that adenosine inhibits neurotransmission between the hippocampus and septum through activation of pre- and postsynaptic A₁-receptors which couple with G-proteins of different PTX-sensitivity or with distinct transduction processes at pre- vs. postsynaptic sites.     

Interaction of age and sex in sympathetic axon ingrowth into the hippocampus following septal afferent damage

Summary Damage to the medial septal nucleus or to the fimbria/fornix in the adult rat elicits sprouting of vascular sympathetic fibers into the deafferented regions of the hippocampal formation. The following study examines the effects of developmental stage and sex on this sprouting phenomenon using both fluorescence histochemistry and high affinity uptake of noradrenaline. We find that (1) the sprouting, which is reduced in adult and juvenile males relative to females, is equivalent in the two sexes after transections at postnatal day 3, and (2) the period of maximum ingrowth is sexually regulated, occurring near postnatal day 3 in the male and postnatal day 13 in the female.     

The distribution of the projection from the hippocampal formation to the nucleus accumbens in the rat: an anterograde- and retrograde-horseradish peroxidase study

We have investigated the distribution and organization of the projection from the hippocampal formation to the nucleus accumbens in the rat. In the first experiments, horseradish peroxidase was injected into the fimbria fornicis. This procedure resulted in massive anterograde labelling of fornix fibers, and enabled the hippocampo--accumbens projection to be charted in detail. Labelled fornix fibers are distributed to the entire length of the nucleus accumbens and do not spread lateral to the anterior limb of the anterior commissure, that is, the projection is limited to the medial nucleus accumbens. Terminal labelling is particularly dense in a caudal dorsomedial sector of accumbens immediately adjacent to the septum. In the second part of the study, horseradish peroxidase was microelectrophoretically injected into the nucleus accumbens, in order to confirm the findings from the anterograde experiments. When the deposit was localized within the fornix distribution field, as indicated by the first experiment, retrogradely-labelled cells were observed in the subiculum, prosubiculum, and to a lesser extent, in hippocampal field CAI. When the deposit was located outside of the fornix distribution field, no hippocampal labelling was noted. The topography of the projection, suggested by the retrograde labelling experiments, is discussed. The findings confirm earlier reports of such a projection from the hippocampal formation to the nucleus accumbens, and with the use of a relatively novel anterograde-horseradish peroxidase technique, provide a picture of fiber labelling representing the entire field of origin of the fornix system. The striatal projection field of this pathway is discussed in relation to other striatal afferents, with particular emphasis on limbic afferentation of the striatum. Finally, the so-called 'hippocampal district' of striatum is discussed with respect to its neurotransmitter composition, as well as its functional importance regarding limbic system influence on central motor mechanisms.     

Biochemical evidence for overlapping neocortical and allocortical glutamate projections to the nucleus accumbens and rostral caudatoputamen in the rat brain

The high affinity uptake of l-glutamate has been used to investigate the origin and distribution of putative glutamate fibers in restricted parts of the rostral caudatoputamen and the nucleus accumbens of the rat brain. Ablation of the frontal cortex reduced the glutamate uptake heavily (?77%) in the dorsal part of the ipsilateral caudatoputamen, but also led to significant decreases in the ventral parts of the ipsilateral caudatoputamen (?62% and ?53%), in the ipsilateral nucleus accumbens (?25% and ?18%) and in the contralateral dorsal part of the caudatoputamen (?21%). Lesion of the caudal neocortex reduced the glutamate uptake in the dorsal part of the ipsilateral caudatoputamen only (?23%). Lesions of the fimbria/fornix reduced the glutamate uptake in both parts of the ipsilateral nucleus accumbens (?46% and ?34%) and by approximately 20% in the whole dorsoventral extent of the anterior caudatoputamen.The results indicate that the frontal neocortex distributes fibers which may use glutamate as neurotransmitter both to the whole ipsilateral caudatoputamen and to the nucleus accumbens, and also to the dorsal parts of the contralateral caudatoputamen. The caudal neocortex probably sends such fibers to the dorsal ipsilateral caudatoputamen, and the caudal allocortex sends such fibers through the fimbria/ fornix to the nucleus accumbens and the ventral part of the ipsilateral caudatoputamen. The results thus corroborate previous suggestions of close similarities between the nucleus accumbens and the ventral caudatoputamen.     

Persistence of sympathetic ingrowth fibers in aged rat hippocampus

Sympathetic fibers appear in the rat hippocampus following interruption of the septal-hippocampal pathway. The current study examined the relative ability of young (3 month) and old (24 month) rats to produce sympathetic ingrowth fibers. Sympathetic ingrowth was present in the hippocampus of young adult rats 2 months after fimbria/fornix transection. The aged rats either lacked, or had very limited, hippocampal ingrowth two months after fimbria/fornix transections. In contrast, aged rats which had fimbria/fornix transections as young adults had extensive hippocampal ingrowth fibers. The topographical distribution of ingrowth fibers in the hippocampal formation was similar in young 3-month-old rats and rats which were lesioned young and sacrificed when aged. Counts of sympathetic fibers found similar numbers of hippocampal ingrowth fibers at both of the post-operative ages. Thus, although aged animals were acutely impaired in their ability to initiate the ingrowth response, the sympathetic fibers which were established at a young age persisted into senescence.     

A comparison of the mode of termination of the hippocampal and hypothalamic afferents to the septal nuclei as revealed by electron microscopy of degeneration

Summary Previous studies with the Nauta technique have established that fibres which originate in two important areas — the hippocampus and the hypothalamus — converge upon the cells of the septal nuclear complex. The purpose of this study was to investigate the anatomical basis of how the septal cells could differentiate between fibres from the two sources. Differences in the mode of termination of these two systems have been studied quantitatively at the electron microscope level by using the orthograde degeneration of terminals after lesions of the fimbria and the medial forebrain bundle. In the medial septal nucleus, the hippocampal fibres account for 35% of the terminals, and in the lateral septal nucleus, 43% of the terminals on the same side and a further 13% on the opposite side. These terminals are at least 98% axodendritic and 91% of them contain predominantly clear synaptic vesicles of 500 Å diameter. The hypothalamic fibres are the source of up to 19% of the axodendritic terminals in the medial septal nucleus, but considerably fewer in the lateral septal nucleus. In contrast to the hippocampal afferents, the hypothalamo-septal system has two characteristic features: firstly, the fibres give rise to up to 24% of the axosomatic terminals in the medial septal nucleus, and secondly, 63% of the terminals contain a population of vesicles with significantly higher proportions of dense centred vesicles of 800–1000 Å diameter.     

Origin of leucine-enkephalin fibers and their two main afferent pathways in the bed nucleus of the stria terminalis in the rat

Summary The destruction of th central amygdaloid nucleus (Ce), which contains a large group of neurons with leucine-enkephalin (L-ENK)-like immunoreactivity (L-ENKI), resulted in a marked ipsilateral reduction of these fibers in the bed nucleus of the stria terminalis (BST) suggesting that L-ENKI neurons in the Ce project ipsilaterally to the BST. This was supported by the finding that injection of biotin-wheat germ agglutinin into the BST labeled many neurons in the Ce. Simultaneous staining with antiserum showed that some of these neurons are L-ENKI. The L-ENKI fibers from the Ce reach the BST via two pathways; one from the ventral amygdalofugal pathway (VA), which terminate in the ventral subdivision of the BST pars lateralis (BSTL), and the other from the stria terminalis (ST), which terminates in the lateral subdivision of the BSTL, because (1) accumulation of L-ENKI structures appeared in the axons of these two systems on the amygdaloid side, (2) transection or destruction of the ST alone caused only a slight reduction of ENKI fibers in the lateral subdivision of the BSTL ipsilaterally and (3) transection or destruction of VA alone markedly reduced the number of L-ENKI fibers in the ventral subdivision of the ipsilateral BSTL. Thus, the VA L-ENKI fiber system is the major source of L-ENKI fibers in the ventral subdivision, while the ST L-ENKI fiber system is a minor source of the L-ENKI fibers in the lateral subdivision. The presence of an intrinsic L-ENKI system in the BST which may innervate the lateral subdivision was also suggested.Abbreviations used in Figures ac anterior commissure - AHy anterior hypothalamic nucleus - AM anteromedial thalamic nucleus - AV anteroventral thalamic nucleus - BST bed nucleus of stria terminalis - BSTL BST pars lateralis - BSTM BST pars medialis - Ce central amygdaloid nucleus - f fornix - GP globus pallidus - HDB horizontal limb of diagonal band of Broca - ic internal capsule - l lateral subdivision of the BSTL - LH lateral hypothalamus - LPO lateral preoptic area - LS lateral septal nucleus - m medial subdivision of the BSTL - Mfb medial forebrain bundle - MPO medial preoptic area - MS medial septal nucleus - ox optic chiasma - Re reuniens thalamic nucleus - Rt reticular thalamic nucleus - SI substantia innominata - sm stria medularis thalami - st stria terminalis - v ventral subdivision of the BSTL - va ventral amygdalofugal pathway - VDB vertical limb of diagonal band of Broca - VP ventral pallium - 2n optic nerve - 3v third ventricle     

Precommissural Fornix in the Human Brain: A Diffusion Tensor Tractography Study

Purpose

Other than a single case report, no diffusion tensor tractography (DTT) studies of the precommissural fornix in the human brain have been conducted. In the current study, we attempted to visualize the precommissural fornix in the human brain using DTT.

Materials and Methods

We recruited 36 healthy volunteers for this study. Diffusion tensor images were scanned using a 1.5-T scanner, and the precommissural fornix was analyzed using Functional Magnetic Resonance Imaging of the Brain (FMRIB) software. Values of fractional anisotropy (FA), mean diffusivity (MD), and tract volume of the precommissural fornix were measured.

Results

The precommissural fornix originated from the hippocampal formation on each hemisphere as a crus; both crura were then joined to the body of the fornix. The body of the fornix continued anteriorly to the level just superior to the anterior commissure, where it divided into each column of the precommissural fornix. Each column descended anteriorly to the anterior commissure and terminated in the septal nuclei. Values of FA, MD, and tract volumes of the precommissural fornix did not differ between the right and left hemispheres (p>0.05).

Conclusion

We believe that the methodology and results of this study would be helpful to future research on the precommissural fornix and in the elucidation of the pathology of diseases involving the precommissural fornix.     

Two populations of rhythmically bursting neurons in rat medial septum are revealed by atropine

1. Previous findings, such as the sensitivity of the hippocampal theta rhythm to cholinergic manipulation, support a "pacemaker" role for the cholinergic cells of the medial septal nucleus and the vertical limb of the nucleus of the diagonal band (MSN-NDB). To explore the mechanism(s) of action of systemic antimuscarinic drugs in eliminating the theta rhythm, recordings of hippocampal EEG and rhythmic MSN-NDB neurons that fired in phase with the hippocampal theta rhythm were taken during the administration of atropine in urethane-anesthetized rats. 2. Twenty-two of 33 rhythmic MSN-NDB cells continued to burst at the theta rhythm frequency after administration of a dose of atropine (25 mg/kg iv) that was sufficient to eliminate the theta rhythm (atropine-resistant cells). The remaining 11 cells lost their rhythmic firing pattern over the same time course as the loss of the theta rhythm (atropine-sensitive cells). 3. Both types of rhythmic MSN-NDB cells could be antidromically driven from the fimbria/fornix with similar latencies (range, 0.5-4.0 ms). The extracellularly recorded spike waveforms were not useful in predicting the atropine sensitivity of a given cell. Atropine-resistant cells frequently had higher firing rates than atropine-sensitive cells, but there was sufficient overlap of the two groups to make this a poor predictor of sensitivity. 4. Cooling the fimbria/fornix reversibly eliminated the hippocampal theta rhythm, but had no effect on 21/25 rhythmic MSN-NDB cells tested. This indicates that the atropine-sensitive MSN-NDB cells do not depend on the periodic output from the hippocampus for their rhythmic firing. Recordings from pairs of rhythmic MSN-NDB cells during cooling and/or atropine administration showed unchanged phase relations at the theta rhythm frequency. In rats in which the septohippocampal system was exposed by aspirating the overlying brain tissue, direct application of atropine (10 mg/ml) to the septal nuclei reversibly eliminated the hippocampal theta rhythm. 5. The rhythmic cells of the MSN-NDB are apparently composed of at least two distinct types, both of which potentially contribute to the production of the theta rhythm in the hippocampus. Elimination of hippocampal theta rhythm after local septal atropine application suggests that the loss of rhythmic activity in the group of atropine-sensitive septal cells is sufficient for the elimination of the theta rhythm. A model of the septohippocampal connections necessary for the theta rhythm is presented.     

Neuronal activity in the subcortically denervated hippocampus: a chronic model for epilepsy

Spontaneous and evoked field potentials and cellular discharges were studied in the subcortically denervated hippocampus of the freely moving rat. The fimbria fornix, the ventral hippocampal commissure, and the supracallosal afferent fibers were removed by aspiration, and recordings were made 3-5 months after the lesion. Two types of spontaneous interictal spikes were observed. Type 1 interictal spike had identical depth distribution to physiological sharp waves but they were shorter in duration (less than 40 ms), larger in amplitude (greater than 2.5 mV) and population spikes were riding on the main deflection. Type 2 interictal spikes were negative in the stratum oriens and positive in the pyramidal layer and stratum radiatum of both CA1 and CA3. The amplitude of both types of interictal spikes could exceed 6 mV. We suggest that interictal spikes were initiated randomly in different subpopulations of the CA2-3 region and the location of the initiating population burst determined the polarity and amplitude of the extracellular interictal spike. Repetitive stimulation of the perforant path (5 Hz, 6 s) evoked markedly uniform afterdischarges in both intact and fimbria fornix-deprived rats. The threshold of afterdischarges was significantly lower, the seizure spread to the contralateral hippocampus was slower, and secondary afterdischarges lasted significantly longer in the lesioned rats. We suggest that under physiological conditions the electrical stability of the hippocampus is ensured by the feed-forward inhibitory action of subcortical afferents. Removal of tonic inhibitory influences and/or sprouting of local axon collaterals allows extreme synchronization and reverberation of information in the entorhinal-hippocampal-entorhinal cortex circuitry. The presence of interictal spikes and increased susceptibility to seizures for several months after the lesion offers the fimbria-fornix-deprived hippocampus a useful chronic preparation to study the mechanisms of limbic epilepsy.     

Frequency-related inhibitory mechanisms controlling rhythmical activity in the septal area.

1. The response patterns of identified neurones in the medical and lateral septal regions to varying rates of repetitive stimulation of the fimbria were investigated in rats anaesthetized with urethane. 2. Neurones in the lateral septum which characteristically respond to single pulse stimulation of the fimbria with an activation-inhibition sequence, exhibited a reduction or complete elimination of the inhibitory component both during and following tetanic volleys delivered at 7-12 HZ. Stimulation at lower frequencies did not alter the response. 3. Concurrently with this effect on the inhibitory component of the response exhibited by lateral septal cells, repetitive volleys eliminate the small amplitude burst discharges which are correlated with the onset of the inhibitory period and are considered to indicate the firing of inhibitory interneurones. 4. Tetanic stimulation of the fimbria at rates which eliminate this interneuronal response in the lateral septum, produce an irregular pattern of firing in medial septal neurones which previously exhibited a synchronized bursting discharge to single pulses. 5. Ipsilateral section of the fimbrial input to the septum resulted in the elimination of the burst discharge pattern exhibited by medial septal neurones. 6. The results suggest that a frequency gating mechanism in the lateral septum, activation of which is dependent upon the level of hippocampal output, is responsible for controlling the firing pattern of medical septal neurones.     

A comparison of supramammillary and medial septal influences on hippocampal field potentials and single-unit activity

1. A comparison was made between the influences of supramammillary (SUM) and medial septal (MS) nuclei on hippocampal physiology in Nembutal-anesthetized rats. Specifically, the effects of prestimulation of the SUM or MS on the perforant path-dentate field potential, on spontaneous activity of single units, and on perforant path-induced unit activation were assessed. Another series of experiments addressed the issue of whether the SUM and MS effects on the perforant path-dentate field response are independent. 2. Prestimulation of the SUM or MS significantly facilitated the perforant path-dentate population spike with no clear effect on the field excitatory postsynaptic potential (EPSP) recorded in the subgranular zone of the dentate hilus. Prestimulation of either nucleus also reduced the threshold for spike onset. The major differences between the two spike facilitation effects were the magnitude of the change and possibly the optimal interstimulus intervals required to obtain the effects. 3. Acute transection of the ipsilateral column of fornix or dorsal fornix eliminated the SUM population spike facilitation effect. MS lesion or dorsal fornix/fimbria transection eliminated the MS spike facilitation effect. The MS lesion did not alter the effects of SUM prestimulation. Cingulum or medial forebrain bundle transection affected neither SUM- nor MS-mediated spike facilitation. Thus the SUM and MS influences on the dentate field response appear to be independent of one another. The relevant SUM afferents travel through the ipsilateral column of fornix and dorsal fornix, whereas MS afferents project through the dorsal fornix/fimbria. 4. Single units recorded in stratum granulosum (SG) were assessed with respect to several parameters. These included the mean firing rate, whether or not excitation occurred prior to the field population spike and at lower threshold, and whether or not a driven unit responded to a second perforant path stimulus delivered at short latency following the first (during the period of population spike depression). The latter parameter in particular appeared to separate SG cells into two classes. The cells that were not activated during the second field potential were classified as granule cells, whereas those that were activated were classified as basket cells. Based on this distinction, significant differences were also found between the two cell classes on the other parameters. In particular, cells classified as granule cells often had very low firing rates.(ABSTRACT TRUNCATED AT 400 WORDS)     

Electrophysiological analysis of the hippocampal-septal projections: II. Functional characteristics

Summary 1. The septum and dorsal hippocampus were exposed in rats by the ablation of the overlying cortex and corpus callosum. The hippocampal efferent system, fornix and fimbria, were stimulated with either single or paired shocks and field potentials, extra- and intra-cellular unitary potentials were recorded in the lateral septal nucleus. 2. The double-shock pairing within the same hippocampal system resulted in facilitation of the monosynaptic test field response. 3. Pairing across systems resulted in long-term suppressions of the mono-synaptic test field response. 4. IPSPs and lack of convergence of excitatory input are responsible for the long-term suppression. 5. It is suggested that the IPSPs are mediated via interneurons, and that some of which at least are activated recurrently. 6. Hippocampal stimulation suppresses the amygdaloid evoked field response for very long periods, often beyond 1000 msec.This study was supported by U.S. Public Health Service Grants RR 5384 and NB 00405.