Dorsal Fornix Research Articles

Electrophysiological properties of identified postnatal rat hippocampal pyramidal neurons in primary culture

Electrophysiological experiments were performed on primary cell cultures of retrogradely labelled postnatal rat hippocampal neurons. Rhodamine microspheres injected into the dorsal fornix clearly labelled the pyramidal cell layer of the hippocampus while excluding the other hippocampal layers and the dentate gyrus. In dissociated cell culture, the labelled cells were easily identified by fluorescence microscopy. Anti-neuron-specific enolase and anti-glial fibrillary acidic protein antibody staining confirmed that the labelled cells were neurons. The input resistance decreased from 2 GΩ to 450 MΩ, the input capacitance increased from 25 pF to 75 pF, the percentage of cells showing repetitive action potentials increased from 6% to 30%, and both peak GABA and glutamate responses increased over 100% during the 0 to 10 days time period investigated. This increase in chemosensitivity can be accounted for by an increase in cell size without an increase in the specific amino acid gated channel density. The subset of hippocampal neurons identified by the retrograde tracer technique are similar to non-labelled neurons with respect to the electrophysiological and pharmacological variables investigated. Nevertheless, it is likely that identified neurons may possess unique properties not evident in this study and refinement of the dissociated cell culture system using identified neuronal subpopulations may facilitate investigations looking at neuronal interactions such as synapse formation.

Nerve growth factor promotes collateral sprouting of cholinergic fibers in the septohippocampal cholinergic system of aged rats with fimbria transection

Nerve growth factor (NGF) was injected intraventricularly into aged (24 months) rats with unilateral fimbria transection. Controls received intraventricular injections of cytochrome c. A quantitative analysis of acetylcholinesterase (AChE)-positive fibers was used to evaluate whether the NGF treatment can stimulate regeneration and reinnervation of the cholinergic axons in the septohippocampal system of aged rats with fimbria transection. A marked increase in the density of AChE-positive fibers was observed in the lateral septum, the dorsal fornix and the dorsal hippocampus of the NGF-treated animals, as compared to the controls. In the lateral septum, the increase was observed in the 2-month NGF-treated animals but not in the 15-day NGF-treated animals. In the dorsal fornix at the level of the dorsal hippocampus, the increase was observed on both the lesioned and unlesioned sides of both the 15-day and 2-month NGF-treated animals. In the denervated (lesioned side) hippocampus, the increase took place in the dorsal hippocampus but not in the ventral hippocampus of both the 15-day and 2-month NGF-treated animals. There was no recovery of AChE-positive fibers on the lesioned side of the fimbria distal to the lesion site even in the 2-month NGF-treated animals. These results demonstrate that intraventricular injections of NGF can stimulate collateral sprouting of intact cholinergic axons in the septohippocampal system and promote cholinergic reinnervation of the denervated hippocampus of aged rats with fimbria transection.

Clonidine reverses spatial learning deficits and reinstates θ frequencies in rats with partial fornix section

Rats received knife-cuts to the dorsal fornix or sham-operations. Half of the animals from each group were injected with clonidine (0.01 mg/kg) and the others with saline before each daily trail of a 10-trial radial 8-arm maze task. The number of choices before the first repetition and the run time were used as performance indices. Lesioned rats were significantly impaired in the acquisition of this task. Clonidine-treated rats, lesioned or not, had an acquisition profile indistinguishable from that of sham-operated saline-injected rats, in spite of their increased run time. When tested one week after the last learning trial in a no-drug condition, lesioned rats treated with clonidine throughout learning maintained a high level of performance during the 5-day retraining phase. A parallel analysis of theta rhythms recorded in an independent group of rats placed in equivalent treatment and/or lesion conditions was then performed. Preoperatively, clonidine injections decreased theta frequency during both alert immobility and movement. Partial fornix lesions produced an increase in theta frequency. Finally, clonidine in fornix-damaged rats decreased theta frequency, thus reinstating the postoperative values at a level statistically no different from that recorded preoperatively. The role of clonidine in restoring the function of the septo-hippocampal input in partially fornix-damaged rats through a noradrenergic modulation of hippocampal acetylcholine release is discussed.

Blockade of behavioral sensitization to methamphetamine by lesion of hippocampo-accumbal pathway

The present studies were carried out to explore a role of the hippocampal efferents in the development of the locomotor augmentation induced by repeated methamphetamine administrations. For this purpose, electrolytic lesions of either the dorsal fornix or the fimbria fornix were made bilaterally in rats. The latter treatment, not the former, blocked the behavioral sensitization. These results suggest that the hippocampo-accumbal pathway may play an important role in the development of the sensitization.

Graft-induced behavioral recovery from subcallosal septohippocampal damage in rats depends on maturity stage of donor tissue

Long-Evans female rats sustained electrolytic lesions of the fimbria and the dorsal fornix and, 10–14 days later, received intrahippocampal suspension grafts of septal-diagonal band tissue from either 14-day-old (Group S14, n = 8) or 16-day-old fetuses (Group S16, n = 10), or of parietal cortex from 16-day-old fetuses (Group Cx, n = 10). Sham-operated (Group S, n = 10) and lesion-only (Group Fifo, n = 21) rats served as non-grafted controls. Spontaneous alternation was assessed in a T-maze at three weeks and two months post-grafting. Home cage and open field activity as well as radial maze learning were assessed from two months post-grafting onwards. Fimbria-fornix lesions induced lasting hyperactivity in both the open field and the home cage, impaired radial maze learning and transiently reduced spontaneous alternation rates. Neither type of graft significantly affected home cage activity. Septal diagonal band grafts improved open field habituation (within trial decline of ambulatory activity) and radial maze learning; the former was observed only in S16 rats, whereas the latter was observed only in S14 rats. Acetylcholinesterase histochemistry revealed an initial lesion-induced depletion of hippocampal acetylcholinesterase (eight days post-surgery) which was no longer observed at the end of the experiment. Acetylcholinesterase positivity was similar in S14 and S16 grafts, which also contained many choline acetyltransferase-positive neurons. Cortical grafts were found to be almost devoid of acetylcholinesterase positivity and no well-stained choline acetyltransferase-positive neurons could be identified. Septal diagonal band grafts from 14-day-old fetuses and cortical grafts contained more parvalbumin-positive neurons than septal-diagonal band grafts provided by 16-day-old fetuses. These results suggest that grafts rich in cholinergic neurons may promote behavioral recovery from fimbria-fornix lesion-induced deficits. However, such a recovery may concern different behavioral deficits as a function of the age of the implanted tissue, suggesting that the maturity stage of the donor may critically influence the functional expression in the lesioned recipient. Also, such a recovery does not appear to be related solely to cholinergic hippocampal (re)innervation and might depend on the presence, not only of cholinergic neurons, but also of non-cholinergic neuronal populations, such as parvalbumin-positive (probably GABAergic) neurons.

Axotomy-dependent stimulation of choline acetyltransferase activity by exogenous mouse nerve growth factor in adult rat basal forebrain

Transection of the adult rat dorsal fornix and fimbria (F-F) induced a sensitivity of the cholinergic neurons in the medial septum and diagonal band (MS/DB) to exogenous mouse nerve growth factor (mNGF). Continuous infusion of mNGF for two weeks after complete unilateral F-F aspiration resulted in a stimulation of choline acetyltransferase (ChAT)-specific activity in precise micro-dissections of the MS/DB ipsilateral to the transection to a level that was 200% higher than that measured in normal adult animals. This supranormal stimulation of ChAT activity reached plateau levels after 10 days of NGF infusion and was dose-dependent with an E.D. 50 equal to 120 ng/day. Administration of mNGF had no effect on the ChAT activity in the MS/DB of normal animals or animals with a unilateral transection of only the supracallosal dorsal septo-hippocampal pathway. Partial transection experiments indicated that a predominant pathway for cholinergic neurons potentially sensitive to exogenous mNGF runs in the paramedian F-F. Administration of mNGF also induced a stimulation of ChAT activity in dissections of the caudate-putamen both ipsi- and contralateral to the infusion cannula. This indicates that unlike the cholinergic projection neurons of the MS/DB, adult cholinergic striatal interneurons are sensitive to exogenous NGF without prior axotomy.

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)

Effects of nicotine on local cerebral glucose utilization in the rat

We used the autoradiographic 2-deoxy-D-[1-14C]glucose (14C-DG) method of Sokoloff to identify brain areas with altered rates of local cerebral glucose utilization (LCGU) in vivo in response to peripheral I-nicotine administration (0.1, 0.3, 1.0, and 1.75 mg/kg, s.c.). Nicotine stimulated LCGU primarily in areas reported to contain nicotine binding sites, indicating that the sites are true receptors. Increases in LCGU of 100% or more over control were obtained in the medial habenula, fasciculus retroflexus, superior colliculus, and median eminence. Substantial stimulation (50-100% increases) also was obtained in the cerebellar vermis, interpeduncular nucleus, and anteroventral and interanteromedial thalamic nuclei. Moderate increases (20-50%) were observed in the reticular nucleus of the medulla, paramedian lobule, nucleus of the spinal tract of the trigeminal nerve, presubiculum, subiculum, red nucleus, ventral tegmental area, substantia nigra, nucleus ambiguus, nucleus tractus solitarius, dorsal lateral geniculate nucleus, mammillothalamic tract, and fornix. The greatest stimulation in most affected areas was obtained with 0.3 mg/kg nicotine administered at 2 min, but not longer, before 14C-DG. Effects of nicotine on LCGU were antagonized by mecamylamine. The findings indicate that the interaction of nicotine with specific binding sites is coupled to cerebral energy metabolism. The distribution of in vivo cerebral metabolic effects of nicotine implicates various brain regions in the behavioral and physiological effects of nicotine.

Effects of physostigmine and d-amphetamine on the behavior of rats with selective fimbria—fornix lesions and intrahippocampal fetal septal cell transplants

Female Long-Evans rats were given electrolytic lesions of either the medial fimbria bilaterally (Fi, n = 24), the dorsal fornix (Fo, n = 24), or both structures (FF, n = 24) at 31 days of age. Ten rats were given sham-operations. Ten days later, half the rats with lesions received bilateral intrahippocampal grafts of embryonic septal cell suspensions (FiT, FoT, FFT, respectively). As already reported in a separate publication (J.C. Dalrymple-Alford, C.R. Kelche, J.C. Cassel, G. Toniolo, V. Pallage, & B.E. Will, 1987, Experimental Brain Research, 210, 115-128), 7 months after transplant surgery, grafted rats were found to be more impaired in an eight-arm radial maze than nongrafted rats. The present report concerns a pharmacological study carried out in the same rats 11 months after grafting. We examined the effects of ip injections of physostigmine (0.01, 0.05, 0.10 mg/kg) and then of d-amphetamine (1.6 mg/kg), as compared with baseline control injections of saline. Just prior to the drug treatments, performances of grafted and nongrafted rats did not differ significantly, but impairments in grafted rats reappeared during subsequent no-injection and saline control trials. Physostigmine failed to affect significantly the performances in rats of any group. d-Amphetamine improved performances in grafted rats with medial fimbria lesions, impaired performances in grafted rats with dorsal fornix lesions, and did not change performances in grafted rats with both lesions, as compared with their respective nongrafted counterparts. Histological analysis revealed variable reinnervation of the host structure and substantial graft-induced lesions of the hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)

Behavioral deficits after intrahippocampal fetal septal grafts in rats with selective fimbria-fornix lesions.

Fetal septal transplants have been shown to promote behavioral recovery in young adult rats with aspiration fimbria-fornix lesions, rats with septal lesions and in intact aged rats. The present study examined the behavioral impact of intrahippocampal septal cell suspension transplants (T) in young female rats that had received, 10 days earlier, either medial fimbria lesions (Group FI.T), dorsal (subcallosal) fornix lesions (Group FO.T) or these two lesions together (Group FIFO.T). Relative to rats with lesions only (groups FI, FO and FIFO), grafted rats, irrespective of lesion locus, displayed unexpected impairments in (i) a serial alternation learning task, 5 weeks and 6 months after transplantation, and (ii) in a radial maze, 7 months after transplantation. In the first alternation test, Group FIFO showed impaired performance relative to Groups FI, FO and the sham-operated controls (Group S). In the second alternation test, Groups FO.T and FO showed impaired performance relative to Groups FI.T and FI, and only the performance of Group FI did not differ from that of Group S. In the radial maze, Groups FI, FO and FIFO all showed impaired performance relative to Group S. By contrast, there were no deleterious effects of lesions or of grafts in the acquisition and retention of a step-through passive avoidance task, 10 weeks after transplantation. Our findings on the effects of selective fimbria-fornix lesions did not confirm the report that rats with FI lesions but not those with FO lesions are unable to learn a serial alternation task, nor the report that FO lesions impair passive avoidance retention. Acetylcholinesterase (AChE) histochemistry revealed that grafts were present but graft-derived innervation of the host hippocampus varied from extensive to almost non-existent in all transplant groups. AChE-positivity in the dorsal hippocampus (DH) was not related to behavioral performance. However, the grafts often grew to a considerable size within the host brain and in many rats, especially those in Group FI.T, produced moderate to extreme damage of the host DH. There was a significant positive correlation between errors in the radial maze and graft-induced DH damage but no relationship between errors and graft size. The results indicate that, after partial lesions of the fimbria-fornix, intrahippocampal septal grafts survive well but are likely to damage recipient structures and result in behavioral impairments.

Parallel modifications of spatial memory performances, exploration patterns, and hippocampal theta rhythms in fornix-damaged rats: Reversal of oxotremorine.

Learning scores and degrees of divergence of the exploratory patterns (EP) displayed during the acquisition stage of a radial eight-arm maze task were examined in fornix-damaged and sham-operated rats injected either with oxotremorine (0.1 mg/kg) or saline. Modifications of hippocampal rhythmic slow activity (theta) recorded in each condition were analyzed in CA1 and dentate gyrus. Dorsal fornix sections reduced choice accuracy but also induced the adoption of weakly divergent EP. Oxotremorine in animals with lesions reinstates both learning scores and degree of divergence of EP at the levels respectively observed in saline sham-operated animals. Finally, oxotremorine in sham-operated animals did not significantly improve choice accuracy but strongly modified the EP. Preoperatively, theta rhythms indicated a decrease of frequency after oxotremorine administration. Postoperatively, they showed an increase of frequency in animals with lesions that were reinstated at the preoperative level by oxotremorine.

Hypothalamic afferent connections mediating adrenocortical responses that follow hippocampal stimulation

This study identified some neural pathways which mediate the adrenocortical responses that follow hippocampal stimulation. The increase in plasma corticosterone following dorsal hippocampus stimulation, in rats with electrodes chronically implanted under pentobarbital anesthesia, was blocked by dorsal fornix and lateral septal lesions and by small posterior hypothalamic deafferentation. Fimbria transection, lateral septal lesions, and posterior hypothalamic deafferentation, but not midbrain reticular formation lesions, also blocked the adrenocortical responses to ventral hippocampus stimulation. Our present and previous studies indicate that the dorsal and ventral hippocampal effects on the hypothalamus, which increase plasma corticosterone concentrations, are mediated by the dorsal fornix and fimbria, respectively, as well as by the lateral septum. A posterior hypothalamic input, which does not involve the medial forebrain bundle or the midbrain reticular formation is also essential for the activation of this response.

Susceptibility to pentylenetetrazol-induced and audiogenic seizures in rats with selective fimbria-fornix lesions and intrahippocampal septal grafts

At the age of 31 days, Long-Evans female rats received electrolytic lesions either of the medial fimbria ( N = 24), of the dorsal subcallosal fornix ( N = 24), or of both structures ( N = 24). Ten rats were used as sham-operated controls. Ten days later, half the rats of each lesion group received intrahippocampal grafts of acetylcholinerich fetal basal forebrain cell suspensions. Twelve months after grafting, all surviving rats, except six grafted rats which became very difficult to handle (because they developed convulsive behavior) were tested for reactivity to pentylenetetrazol (30 mg/kg, i.p.) and to sound (120 dB, 90 s). Grafted rats were found to be more reactive to the drug and less reactive to sound than their nongrafted counterparts with similar lesions. Reactivity to pentylenetetrazol of grafted rats was correlated with body weight and extent of graft-induced hippocampal damage, but not with graft size. Reactivity to sound, which was apparently not dependent on hippocampal damage or graft size, might be related to enhanced graft-derived cholinergic activity in the hippocampus. Our results show that intrahippocampal septal grafts interfere in opposite directions with the seizure-inducing treatments used, so that it can be assumed that the physiologic mechanisms by which grafts do so and by which these treatments induce seizures are likely to be different.

Noradrenergic, serotonergic, and cholinergic sprouting in the hippocampus that follows partial or complete transection of the septohippocampal pathway: Contributions of spared inputs

The aminergic and cholinergic fibers innervating the hippocampus reach their target regions via the dorsal (dorsal fornix, fimbria, and cingulum) and ventral routes. The plasticity of this innervation after lesions of the dorsal pathway was investigated in the septal, medial, and temporal regions of the adult rat hippocampus. The extent and time course of sprouting was assessed by determining high-affinity uptake of [ 3H]noradrenaline and [ 3H]serotonin, and the activities of cholinergic enzymes 1 week to 6 months after partial or complete transection of the dorsal pathway. The initial decline in these terminal indices resulting from the transection of the medial or lateral half of the dorsal pathway reflected the distribution of their respective terminal sites in the three hippocampal regions. Longer survival after such lesions led to a substantial recovery of cholinergic and noradrenergic markers indicating reinnervation of the hippocampus by spared dorsal and/or by undamaged ventral afferent fibers. Whether the recovery was complete or not, the sprouting of spared dorsal fibers was maximum within a relatively shorter postlesion survival whereas that of the ventral afferents continued for a longer time. In contrast to the extent of noradrenergic and cholinergic restitution, very poor serotonergic recovery was seen in the same animal in spite of the availability of spared serotonergic afferent fibers and regardless of the duration of postlesion survival. The apparently finite capacity of spared axons for postlesion reinnervation was not increased by longer survival. Amplification of this property of central neurons by other interventions may supplement the approach of transplantation for recovery of function following injury.

Hippocampofugal γ-aminobutyric acid (GABA)-containing neuron system in the rat: a study using a double-labeling method that combines retrograde tracing and immunocytochemistry

Using a double-labeling method that combines retrograde tracing and immunocytochemistry, we demonstrated the presence of a hippocampofugal γ-aminobutyric acid (GABA)-like immunoreactive (GABA-LI) neuron system in the rat. As a preliminary experiment, knife-cut of the dorsal fornix was made and it resulted in a remarkable accumulation of GABA-LI fibers caudal to the section. This suggested the presence of a hippocampofugal GABAergic projection. The hypothesis was confirmed by the double-labeling method: injection of the biotinylated wheat germ agglutinin (B-WGA) into the septum resulted in labeling numerous neurons in the hippocampus and some of them also showed GABA-like immunoreactivity by the simultaneous immunostaining with the antiserum against GABA.

Influence of endogenous and exogenous growth factors on choline-acetyltransferase (ChAT) activity in rats with fimbria-fornix lesions and acetylcholine-rich transplants in the hippocampus

Long-Evans female rats sustained electrolytic lesions of the fimbria and the dorsal fornix and, two weeks later, received intrahippocampal suspension grafts of fetal tissue. The grafts were prepared from regions including either the medial septum and the diagonal band of Broca (septal grafts), or the mesencephalic raphe (raphe grafts), or from both these regions together (co-grafts). All rats were submitted to a series of behavioural tests (home cage and open-field locomotion, spontaneous alternation, radial-arm maze and Morris water maze performance) run over two periods after grafting (one to nine weeks and 20–35 weeks). Two weeks after completion of behavioural testing, histological (acetylcholinesterase and Cresyl Violet staining) and/or neurochemical (choline acetyltransferase activity, high-affinity synaptosomal uptake of choline and serotonin, noradrenaline, serotonin and 5-hydroxyindolacetic acid concentrations) verifications were performed on the hippocampus.Compared to sham-operated rats, lesion-only rats exhibited hyperactivity which was transient in a familiar environment (home cage) and lasting in an unfamiliar one (open field), decreased rates of spontaneous T-maze alternation, and impaired memory performance in both the radial-arm maze and the Morris water maze. These rats also snowed decreased cholinergic and serotonergic markers with a maximal depletion in the septal two-thirds of the hippocampus. Noradrenaline concentration tended to be increased in the dorsal third of the hippocampus, but was not modified in the other two-thirds.While septal grafts specifically increased the cholinergic markers and raphe grafts the serotonergic ones, neither of these grafts produced a lasting effect on any behavioural variable. Conversely, the co-grafts, which increased both the cholinergic and serotonergic markers in the septal two-thirds of the hippocampus, completely normalized the Morris water maze probe trial performance, but failed to affect any of the other behavioural variables.Our present results confirm that grafts of fetal neurons injected into the denervated hippocampus may induce a neurochemical recovery that depends on the anatomical origin of the grafted cells, and that co-grafting two fetal brain regions allows the combination of their individual neurochemical properties. Furthermore, our results show that these neurochemical effects of the co-grafts may be involved in the recovery of behavioural function observed in the water maze. However, somewhat paradoxically, those effects appear inefficient for inducing any recovery in other behavioural tasks, even in the radial-arm maze, which is assumed to measure similar spatial functions. Finally, it is suggested that the co-grafts might be more efficient in attenuating the spatial reference memory (Morris water maze) rather than the spatial working memory (radial maze) deficits subsequent to fimbria-fornix lesions.

Properties of mapping induced by fornix damages: Learning and memorizing the radial maze task

A correlational analysis of learning scores and degrees of divergence of the patterns of choice was performed in fornix-damaged, sham-operated, and control rats during the acquisition stage of the radial maze task. The results show that dorsal fornix sections, which initially reduce choice accuracy, induce the parallel adoption of weakly divergent patterns of choice. The positive correlation observed during the course of training between these two dependent variables suggests that fornix-damaged animals learn the task on the basis of specific gathering and processing of information: initial choice of few proximal paths with progressive increases in the number of visited paths under the control of reinforcement determines a correlative increase in the degrees of divergence of the patterns of choice. This observation indicates that mapping in lesioned animals occurs through the progressive introduction of new spatial elements in an initial sectorial exploratory system, whereas sham-operated and control animals immediately process more information on the total configuration of the apparatus. This particular gathering and processing of spatial information could determine specific reference and working memory processes in lesioned animals.

Selective lesions of the fimbria and the fornix in the rat: Differential effects on CA1 and dentate theta

The effects of electrolytic lesions of the dorsal fornix and the dorsomedial fimbria on the CA1 and the dentate theta rhythms (θs) recorded from the dorsal hippocampal formation were investigated in the ether-anesthetized rat. The results showed that (i) fornix lesions mainly affected CA1 θ, (ii) fimbrial lesions mainly affected dentate θ, and (iii) combined fornix-fimbria lesions suppressed both CA1 and dentate θs. When considered in connection with other observations, these data suggest that the septal projections pacing the CA1 θ may course essentially within the dorsomedial fornix whereas those pacing the dentate θ may pass essentially within the dorsomedial fimbria. Moreover, our data provide new support for the hypothesis that at least two septohippocampal neural systems are anatomically and functionally independent and capable of controlling the θ activity of the dorsal hippocampal formation of the anesthetized rat.

Posterior hypothalamic deafferentation abolishes the amnestic effect of electroconvulsive shock in rats

The amnestic effect of immediate post-training transcorneal electroconvulsive shock ECS (15.0 mA, 60 Hz, 2 sec) on step-down inhibitory avoidance learning (0.5 mA, 60 Hz training footshock) was studied in intact rats and in rats submitted to bilateral surgical transection of the dorsal fornix, to anterior or posterior hypothalamic deafferentation, and in sham-operated animals. Animals were tested for retention 24 hr after training. The amnestic effect of ECS was observed in all groups except in the one with the posterior hypothalamic lesion. Fornix-lesioned animals showed a moderate retention deficit which was considerably worsened by the ECS treatment. The results indicate that the amnestic effect of ECS requires integrity of posterior hypothalamic pathways. One possibility is that the amnestic effect of ECS may be mediated by posterior afferent fibers to the hypothalamus acting on hypothalamic opioid systems such as have been previously proposed to play a role in ECS-induced amnesia.

Response of the rat brain β-endorphin system to novelty: Importance of the fornix connection

In control rats, a step-down inhibitory avoidance training trial using a 0.8 mA footshock, or simple exposure to the training apparatus without footshock, was followed by a decrease of beta-endorphin-like immunoreactivity measured in the hypothalamus and ventral thalamus. The effect of inhibitory avoidance training was also measured in rats submitted to a brain sham operation, to bilateral transection of the dorsal fornix, to anterior or to posterior hypothalamic deafferentation, to adrenal medullectomy, to an adrenal sham operation, to 16 daily ip injections of 0.2 mg/kg dexamethasone, or to 16 daily ip injections of 1 ml/kg saline. The diencephalic beta-endorphin-like immunoreactivity response to training was abolished by fornix transection and was unaffected by all other treatments. This suggests that the response is not mediated by anterior or posterior neural afferents to the hypothalamus, or by a hypersecretion of epinephrine by the adrenal medullae, or of ACTH by the pituitary gland. The response, instead, appears to require the integrity of the pathway that sends projections from the septo-hippocampal system to the hypothalamus. Previous evidence had suggested that the diencephalic beta-endorphin-like immunoreactivity response to training is a result of novelty, and the septo-hippocampal system has been postulated to play a role in the registration of novelty.