Intraseptal Injection Research Articles

Retrograde labeling of rat dorsolateral septal nucleus neurons following intraseptal injections of WGA-HRP.

Projection neurons in the rat dorsolateral septal nucleus (DLSN) were retrogradely labeled following intraseptal injection of wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP). Injections of WGA-HRP centered in the medial septum (MS) and parts of the intermediate and ventrolateral subdivisions of the lateral septum retrogradely labeled only a few centrally scattered multipolar-shaped neurons. In contrast, injections placed in the nucleus of the diagonal band of Broca (DBB) consistently resulted in labeling of DLSN neurons of all sizes and shapes. Large injections in rostral DBB appeared to retrogradely label every DLSN neuron, while similar injections in caudal DBB only labeled neurons in restricted regions of the nucleus. A collection of small cells forming the ventricular border of caudal DLSN and a group of larger cells situated in the dorsolateral tip of rostral DLSN were consistently labeled following each DBB injection. The pattern of retrogradely labeled neurons in the DLSN appeared in a complementary fashion to that seen in the other lateral septal nuclei. Our findings support the conclusion that the DLSN is a morphologically heterogeneous nucleus consisting almost entirely of projection neurons. The pattern of retrograde labeling in the lateral septum suggests that these projection neurons may be topographically organized since distinct subpopulations of cells were labeled following different injections in the MS/DBB complex.

Retrograde labeling of rat dorsolateral septal nucleus neurons following intraseptal injections of WGA‐HRP

Projection neurons in the rat dorsolateral septal nucleus (DLSN) were retrogradely labeled following intraseptal injection of wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP). Injections of WGA-HRP centered in the medial septum (MS) and parts of the intermediate and ventrolateral subdivisions of the lateral septum retrogradely labeled only a few centrally scattered multipolar-shaped neurons. In contrast, injections placed in the nucleus of the diagonal band of Broca (DBB) consistently resulted in labeling of DLSN neurons of all sizes and shapes. Large injections in rostral DBB appeared to retrogradely label every DLSN neuron, while similar injections in caudal DBB only labeled neurons in restricted regions of the nucleus. A collection of small cells forming the ventricular border of caudal DLSN and a group of larger cells situated in the dorsolateral tip of rostral DLSN were consistently labeled following each DBB injection. The pattern of retrogradely labeled neurons in the DLSN appeared in a complementary fashion to that seen in the other lateral septal nuclei. Our findings support the conclusion that the DLSN is a morphologically heterogeneous nucleus consisting almost entirely of projection neurons. The pattern of retrograde labeling in the lateral septum suggests that these projection neurons may be topographically organized since distinct subpopulations of cells were labeled following different injections in the MS/DBB complex. © 1996 Wiley-Liss, Inc.

Intraseptal administration of (1 S,3 R)-1-aminocyclopentane-1,3-dicarboxylic acid induces immediate early gene expression in lateral septal neurons

Prior work has shown that activation of metabotropic glutamate receptors can induce burst firing and a form of NMDA receptor independent long term potentiation in lateral septal slice preparations. To study this phenomenon in vivo we used the expression of immediate early gene products as markers for increased neuronal activity following intraseptal injection of the metabotropic agonist 1 S,3 R-ACPD. Intraseptal injection of 1 S, 3 R ACPD induced the expression of Fos-like, Jun 13-like and Krox24-like immunoreactivity in lateral septal neurons in a dose-dependent fashion. Immediate early gene product expression peaked at 4 to 6 h post-injection and then declined to baseline. Immediate early gene expression was diminished by co-injection of l-AP3 and was not elicited by intraseptal injection of l-AP4, cysteine sulfinic acid or DHPG. Immediate early gene expression was not diminished by chronic lithium treatment but was diminished by chronic treatment with the phospholipase A 2 inhibitor quinacrine. Co-injection of the phospholipase AZ inhibitor NDGA partially suppressed the induction of immediate early gene expression. Metabotropic glutamate receptors regulate lateral septal neuron excitability in vivo and some of their effects may be mediated by activation of phospholipase A 2. Alternatively, arachidonic acid may play a permissive role it the effects of metabotropic glutamate receptors on lateral septal neurons.

Effects of reversible inactivations of the medial septal area on reference and working memory versions of the Morris water maze

Involvement of the medial septal area (MSA) in reference memory and working memory versions of the Morris water maze (MWM) task was investigated in rats with reversible inactivation of this area by drugs injected through a single cannula aimed at the MSA. In Experiment 1, rats were trained in a reference memory version of the MWM with two blocks of four trials per day for 3 consecutive days. Acquisition was impaired by pretrial MSA injection of 10 ng tetrodotoxin (TTX) in 1 μl saline but not of saline alone into MSA. In Experiment 2, intraseptal injection of TTX (10 ng, 1 μl) immediately after two blocks of four trials had no effect on the consolidation of spatial reference memory. In Experiment 3, intraseptal injection of TTX (10 ng, 1 μl) impaired retrieval of well established spatial reference memory in rats which had received 8 trials per day for 3 consecutive days. In Experiments 4 and 5, rats were trained in a working memory version of MWM task to find a new target position in trial 1 and retrieval of this information was tested 75 min later in trial 2. Intraseptal injection of lidocaine (4%, 1 μl) prior to training impaired working memory performance while immediately posttraining injection of lidocaine had no effect. It is concluded that normal activity of the MSA is necessary for the memory formation at the time of training but its involvement in posttraining consolidation is unlikely. The MSA function is required for retrieval of well established spatial reference memory.

Reversible inactivation of the medial septal area impairs consolidation but not retrieval of passive avoidance learning in rats

Involvement of the medial septal area (MSA) in consolidation and retrieval of passive avoidance response (PAR) was investigated with functional suppression of this area by tetrodotoxin (TTX). Rats carrying a chronically implanted cannula aimed at the MSA were trained on a step-through passive avoidance task and received intraseptal injection of 5 ng TTX dissolved in 1 μ1 saline 5, 90 and 360 min after the acquisition trial or 60 min before the retrieval test. TTX injected 5 and 90 min after the acquisition trial significantly reduced avoidance of the dark compartment in comparison with the control group injected with saline. PAR was not impaired by septal TTX injected 360 min after acquisition or 60 min before the retrieval test. Step-through latency of naive rats was not affected by septal blockade. The results indicate that the MSA contributes to PAR consolidation at least 90 min after acquisition but its involvement in PAR retrieval is unlikely. It is concluded that functional ablation of the MSA may disrupt integrity of subcortical circuits participating in PAR learning.

Distinct Profile of Working Memory Errors Following Acute or Chronic Disruption of the Cholinergic Septohippocampal Pathway

The behavioral effects of two amnestic treatments (intraseptal chlordiazepoxide (CDP) and intraventricular AF64A) were examined in a delayed-nonmatch-to-sample radial-arm maze (DNMTS) paradigm. The types of errors induced by these treatments in this working memory task were assessed to determine how acute and chronic disruptions of the medial septum affect different phases of working memory (encoding, maintenance, retrieval). Rats were initially trained to perform the DNMTS task with a 1-h delay imposed between the training and the testing sessions. The first experiment demonstrated that intraseptal injection of 30 nmoles of CDP did not produce state-dependent learning. Rats were injected immediately following training with CDP or artificial cerobrospinal fluid (CSF; drug vehicle) and then prior to testing with CDP or CSF. Injection of CDP immediately following training (CDP–CSF) impaired performance of the task regardless of whether CDP was also administered before the postdelay test (CDP–CDP). Rats infused with CDP only before the postdelay test (CSF–CDP) exhibited a proactive deficit characterized by intact retention of the predelay information (i.e., arms entered prior to the delay) but impaired performance on the postdelay component (arms entered only after the delay). These data indicate: (i) that state dependency does not explain the working memory deficits induced by intraseptal CDP; (ii) that pretest CDP disrupts the storage and utilization of working memory for current arm selections. The second experiment examined the behavioral effects induced by a permanent disruption of the cholinergic septohippocampal pathway produced by icv injection of the cholinotoxin AF64A. Rats were initially trained on the DNMTS task and then bilaterally injected icv with either AF64A (2.5 nmoles/side) or CSF. AF64A-treated rats exhibited a significant impairment of performance compared to CSF-treated controls. In contrast to the impairment exhibited by CDP-treated rats in Experiment 1, the performance of AF64A-treated rats displayed a deficit in the maintenance/retrieval of information acquired during RAM trainingandan impairment in ability to store current spatial information in working memory to guide postdelay testing performance. These studies demonstrate that acute and chronic disruptions of the septohippocampal pathway produce distinct profiles of cognitive impairment that should help to reveal the behavioral and neurobiological characteristics of spatial memory.

Glucose injections into the medial septum reverse the effects of intraseptal morphine infusions on hippocampal acetylcholine output and memory

Morphine infusions into the medial septum produce memory deficits which can be attenuated by concurrent intraseptal injections of glucose. The mnemonic deficits following intraseptal morphine injections may be due, in part, to opioid inhibition of cholinergic neurons projecting to the hippocampus, with glucose reducing the effect. The present experiment determined whether glucose injections into the medial septum attenuate the effects of intraseptal morphine injections on hippocampal acetylcholine release and on memory. Samples of extracellular acetylcholine levels were assessed at 12 min intervals using in vitro microdialysis with high-performance liquid chromatography with electrochemical detection. Intraseptal morphine injections (4.0 nmol) reduced acetylcholine output starting at 12 min and lasting up to 72 min post-injection. Glucose (18.3 nmol) injected concomitantly with morphine reversed the drug infusions in the septum 20 min prior to spontaneous alternation testing. Intraseptal morphine infusions reduced alternation scores; this behavioral effect was reversed by concurrent glucose infusions. The effect of drugs infused into the septal area on spontaneous alternation performance and acetylcholine output were positively correlated. These findings suggest that memory deficits induced by intraseptal morphine injections may result, at least partially, from a decrease in the activity of cholinergic neurons and that this effect is reversed by glucose.

Intraseptal injection of caffeine enhances acetylcholine release in the hippocampus of freely moving rats

Intraseptal injection of caffeine enhances acetylcholine release in the hippocampus of freely moving rats

A single intraseptal injection of nerve growth factor facilitates radial maze performance following damage to the medial septum in rats

Rats were trained on a radial maze and then given electrolytic lesions of the MS followed by a single intraseptal injection of 5 μg of NGF. Three days later they were re-tested on the maze. They were also post-operatively tested for hyperemotionality. MS lesions severely impaired performance on the radial maze and produced increased emotionality. MS lesions also produced a general decrease in hippocampal high affinity choline transport and acetylcholinesterase staining, which was not affected by NGF administration. NGF treatment ameliorated the behavioral deficit in the radial maze but had no effect on the hyperemotionality. In order to determine whether the NGF was working to restore previously learned spatial abilities, the type of learning strategy used by the animals was also assessed. NGF treatment did not restore previously learned spatial strategies but facilitated recovery of alternative learning strategies. The reduction in cognitive deficit was also paralleled by reduced ventricular enlargement in the NGF treated rats. The present results suggest that a single injection of NGF can produce a long-lasting improvement on a cognitive task and reduce some of the injury-induced, secondary reactive changes that occur following electrolytic MS lesions.

Pyruvate infusions into the septal area attenuate spontaneous alternation impairments induced by intraseptal morphine injections.

Glucose infusions into the medial septal area attenuate memory impairments produced by concurrent intraseptal morphine injections. One possible explanation for these effects of glucose on memory is that the treatment modulates regional energy metabolism. As a test of this hypothesis, the present experiment determined whether intraseptal pyruvate injections could attenuate a spontaneous alternation impairment seen after intraseptal morphine injections. Intraseptal injections of morphine (4.0 nmol) 30 min prior to testing produced spontaneous alternation scores significantly lower than those in control groups. Morphine injections near, but outside, the septal region did not impair spontaneous alternation performance. The morphine-induced impairment was similarly reversed by coadministration of either glucose (18 nmol) or pyruvate (18 nmol) into the septum. These findings suggest that glucose may act through the tricarboxylic acid cycle by increasing the availability of ATP, augmenting the synthesis of certain neurotransmitters, or both.

Pressor effects of acetylcholine injected into the lateral septal area of conscious rats

Injections of acetylcholine (ACh) into the lateral septal area (LSA) caused blood pressure increases in unanesthetized freely moving rats. ACh was injected in the dose range of 0.1–54 nmol/500 nl using regular metal needles (200 μm o.d.). In the LSA, injections of carbachol or ACh (2.5 nmol/500 nl) were equipotent ( + 22 ± 2 and + 19 ± 3 mmHg, respectively) suggesting the existence of an ACh-sensitive pressor site in the LSA. Maximum responses to ACh injected either intracerebroventricularly (i.c.v.) or into the LSA were not significantly different ( + 23 ± 1 and +21 ± 2 mmHg, respectively). However, the ED 50 for the injection into the LSA (0.24 nmol) was significantly lower than that observed after i.c.v. injection (2.6 nmol), ruling out a possible leakage of ACh from the LSA and into the ventricular space. This idea is supported by data showing that the effect of the intraseptal injection of 30 nmol of ACh was blocked by pretreatment with 3 nmol of atropine either i.c.v. or into the LSA, whereas the effects of i.c.v. ACh were completely blocked by i.c.v. atropine, but only partially (42%) when atropine was injected into the LSA. The idea of the existence of an ACh-sensitive site in the LSA is further supported by the more direct observation that injections of 30 nmol/100 nl of ACh into the LSA using glass needles (50–70μ m o.d.) caused similar pressor responses. Neither the i.v. pretreatment with pentolinium or adrenalectomy affected the response to 30 nmol/500 nl of ACh injected into the LSA, ruling out the involvement of the sympathetic nervous system. The responses to ACh injected either i.c.v. or into the LSA were blocked by i.v. pretreatment with the vasopressin antagonist d(CH2)5Tyr(Me)-vasopressin. In addition, the response to ACh injected into the LSA was also blocked by hypophysectomy, further suggesting a major involvement of circulating vasopressin. The pressor response to intraseptal ACh was significantly reduced by local pretreatment with pirenzepine or 4-DAMP at the equimolar dose of 6.7 nmol, confirming the involvement of M 1-muscarinic receptors in the pressor response to ACh. The existence of a cholinergic muscarinic mechanism in the LSA that mediates pressor responses through the release of vasopressin is proposed.

Task-dependent effects of intra-amygdala morphine injections: attenuation by intra-amygdala glucose injections

Intraseptal injections of morphine impair learning and memory in rats, and these impairments are reversed by intraseptal injections of glucose. With evidence that injections of morphine into the amygdala also impair memory for some tasks, the present experiment determined whether (1) intra-amygdala morphine injections impair performance in inhibitory avoidance and spontaneous alternation tasks, and (2) intra-amygdala glucose injections attenuate the effects of intra-amygdala morphine injections. Rats receiving bilateral injections of morphine (4.0 nmol) into the amygdala, 30 min prior to training in inhibitory avoidance, had retention latencies significantly lower than those of unoperated and CSF controls when tested 24 hr later. Bilateral morphine injections (4.0 or 8.0 nmol) 30 min prior to testing in a spontaneous alternation task did not alter performance. The morphine-induced impairment observed in inhibitory avoidance was not due to diffusion up the cannulas, altered sensitivity to shock, or seizure activity. A glucose dose of 16.67 nmol, but not 8.33 nmol, injected into the amygdala attenuated the morphine-induced deficit in inhibitory avoidance. Rats receiving CSF into the amygdala exhibited decreased retention latencies in inhibitory avoidance compared to those of unoperated controls. This decrease was not attenuated by glucose at doses of 8.33 and 16.67 nmol. Therefore, these findings suggest that the amygdala is another brain region in which glucose affects brain functions, possibly by interacting with the opioid system and/or other neurotransmitter systems.

Effects of intraseptally injected glutamatergic drugs on hippocampal sodium-dependent high-affinity choline uptake in “naive” and “trained” mice

We have previously reported that spatial reference memory (RM) training-induced alterations in hippocampal cholinergic activity as measured by sodium-dependent high-affinity choline uptake (SDHACU). Each training session was found to induce an immediate (30 s) increase in SDHACU followed (30 s to 15 min posttest) by a deactivation and long-lasting inhibition (15 min to 24 h) of this cholinergic marker. The present experiments were designed to assess the role of septal glutamatergic receptors in this posttraining cholinergic deactivation. In the first experiment, the effects of intraseptal injections of different doses of glutamic acid and glutamatergic antagonists (kynurenic acid, KYN, and AP5) on hippocampal SDHACU were studied in awake but otherwise resting (i.e., naive) mice. The results showed that glutamic acid at the lowest dose used (5 ng) produced a decrease in SDHACU, whereas both glutamatergic antagonists produced a dose-related increase in this cholinergic marker. It was concluded that septal glutamatergic receptors mediate a tonic inhibitory input on the cholinergic cells. Hence, in a second experiment the effect of intraseptal injections of KYN (5 ng) on the training-induced changes in hippocampal cholinergic activity were assessed following variable amounts of radial maze RM training. Trained mice were injected 20 min before the first or the ninth training session and killed 30 s or 15 min posttraining for determination of SDHACU. KYN slowed the posttesting cholinergic deactivation (disinhibition), this effect being more marked in good learners than in bad learners. The present findings suggest that septal glutamatergic receptors mediate an inhibitory input on the cholinergic cells, and that this input could play a role in memory consolidation.

Effects of intraseptally injected noradrenergic drugs on hippocampal sodium-dependent-high-affinity-choline-uptake in ‘resting’ and ‘trained’ mice

It has been shown in numerous studies that memory testing can alter presynaptic cholinergic activity within the hippocampus. In the present experiments, the role of the noradrenergic input to the septal cholinergic neurons in the immediate increase in cholinergic activity induced by the first training session of a spatial reference memory task in an 8-arm radial maze was investigated. The effects of bilateral intraseptal injections of noradrenergic drugs on hippocampal sodium-dependent-high-affinity-choline-uptake (SDHACU) were studied in ‘resting’ animals (basal level) or in ‘trained’ animals injected 20 min before training and sacrificed immediately after the test. The results showed that: (1) the injection of maprotiline, a noradrenaline 3euptake inhibitor (0.06 ng/site), induced an increase in hippocampal SDHACU in ‘resting’ animals, whereas the α 2-adrenoceptor agonist UK 14304 (1.5 ng) significantly reduced the basal level of SDHACU; (2) none of the α-adrenoceptor antagonists used (phenoxybenzamine, 10 and 100 ng; BE 2254, 100 and 500 ng; yohimbine, 0.5 and 50 ng) significantly affected the basal level of hippocampal SDHACU, and only the α 1-adrenoceptor antagonist BE 2254 (500 ng) significantly reduced the testing-induced activation of SDHACU. Taken together, these findings suggest that noradrenaline may exert a bimodal regulatory influence on the activity of septo-hippocampal cholinergic neurons. The behavior-induced activation of hippocampal SDHACU could be partly mediated by the stimulation of α 1-adrenoceptors, whereas postsynaptic α 2-adrenoceptors may be important for the maintenance of a tonic inhibition of the steady-state cholinergic activity in the hippocampus. These results are further evidence for a regulatory noradrenergic influence on the activity of septal cholinergic neurons.

Baclofen produces dose-related working memory impairments after intraseptal injection

Altering the activity of the septohippocampal pathway can impair spatial memory in rats. Pharmacological manipulation of septal GABA-A receptors with the agonist, muscimol, or the benzodiazepine agonist, chlordiazepoxide, also impairs spatial memory and depresses hippocampal cholinergic activity. The present experiment examined the effects of intraseptal infusion of the GABA-B agonist baclofen on the performance of rats on a working memory radial arm maze (RAM) task. Post-training administration of baclofen (3 nmol, but not 1.5 or 0.75 nmol) produced a significant impairment of RAM performance. Baclofen significantly reduced the number of correct choices and increased the number of errors committed during testing without affecting latency per arm choice or the ability of the rats to navigate the maze and consume food pellets. The data suggest that baclofen impaired retention of the task without producing proactive performance deficits. Furthermore, the present data are consistent with the hypothesis that a GABAergic mechanism in the medial septum modulates the maintenance or retrieval of spatial working memory.

Thermoregulatory responses following injection of 5-hydroxytryptamine into the septohippocampal complex in rats

The present study investigated the change in thermoregulatory responses following microinjection of 5-hydroxytryptamine (5-HT) into the lateral septum and the hippocampus of unanesthetized, unrestrained rats. Intraseptal injection of 5-HT (5 to 20 μg) caused a dose-related fall in core temperature (T b), which was associated with a decrease in heat production (HP). As the decrease in HP can not completely account for the magnitude of the decrease in T b, increase in heat loss may also be involved in the 5-HT-induced hypothermia. In contrast to observed changes following intraseptal injection, no significant change in either T b or HP was observed after microinjection of the same doses of 5-HT into the hippocampal areas, indicating that the hypothermic response to intraseptal injection of 5-HT is site specific. Further, the hypothermic response to intraseptal injection of 5-HT was only attenuated by systemic pretreatment with cyproheptadine, but not by naloxone or scopolamine, indicating that the hypothermic response is mediated by 5-HT receptor, but not by endogenous opioid and cholinergic systems.

Intraseptal injection of GABA and benzodiazepine receptor ligands alters highaffinity choline transport in the hippocampus

Injection of GABA and benzodiazepine (BDZ) agonists and antagonists into the medial septum produced bidirectional alterations in hippocampal high-affinity choline transport (HAChT). Male Sprague-Dawley rats were injected in the medial septum with either drug vehicle, a BDZ agonist, antagonist, or inverse agonist, or with a GABA-A or GABA-B agonist or antagonist and sacrificed l h later for assessment of HAChT in hippocampal synaptosomes. The GABA-A agonist muscimol, the GABA-B agonist baclofen, and the BDZ agonist chlordiazepoxide (CDP) produced dose-related decreases in HAChT 1 h following injection into the septum. The muscimol-induced decrease in HAChT was prevented by prior intraseptal injection of the GABA-A antagonist, bicuculline. Intraseptal injection of GABA-A (bicuculline) or GABA-B (2-hydroxysaclofen) antagonists did not alter HAChT, whereas the BDZ antagonist flumazenil (RO15,1788) and the BDZ inverse agonist methyl-β-carboline-3-carboxylate (gb-CCM) increased this measure up to 30% in a dose-dependent manner. These results demonstrate that cholinergic neurons in the medial septum can be modulated in a bidirectional way through the pharmacological manipulation of GABA-A, GABA-B, and BDZ receptors. The potential functional and therapeutic consequences of these interactions are discussed.

Spontaneous alternation and inhibitory avoidance impairments with morphine injections into the medial septum. Attenuation by glucose administration

Peripheral glucose administration attenuates impairments produced by peripheral injections of the opioid agonist, morphine, on spontaneous alternation. Injections of opioid agonists directly into the medial septum also impair memory. The present experiments examined whether systemic and intraseptal glucose injections could attenuate deficits on spontaneous alternation and inhibitory avoidance in rats treated with intraseptal morphine. Morphine (3.95 nmol) injected into the medial septum significantly impaired performance on spontaneous alternation and inhibitory avoidance tasks. Both systemic (100 mg/kg, i.p.) and intraseptal (18.33 nmol) injections of glucose, administered concomitantly with intraseptal morphine, attenuated the morphine-induced impairments on these tasks in rats. These findings suggest that one brain region where glucose may act is the medial septum, possibly by releasing opioid inhibition of cholinergic activity.

GABAergic mediation of indirect transsynaptic control over basal and spatial memory testing-induced activation of septo-hippocampal cholinergic activity in mice

A neurochemical study of the transsynaptic interactions established between septal GABAergic interneurones and cholinergic septo-hippocampal neurones was conducted using mice. The effects of acute in vivo injections of either muscimol (20-500 ng/0.2 microliter), bicuculline (100 ng-1 micrograms/0.2 microliter) or saline vehicle (0.2 microliter) into the medial septum on septo-hippocampal cholinergic activity were evaluated using measures of hippocampal high affinity choline uptake at 30 min post-injection in two main groups of mice. The first (quiet control) remained in their home cages during the post-injection period whereas the second (active) were submitted, 10 min following injection to a 20-min period of spatial working memory testing in an 8-arm radial maze. Intraseptal injections of either muscimol or bicuculline produced significant (25-50%) inhibition of hippocampal cholinergic activity in quiet conditions (basal) as compared to intact or saline-injected mice. In the active groups, whereas memory testing induced significant cholinergic activation (+15-20%) in intact and saline injected mice at 30 s post-test no significant memory testing-induced activation was observed in either muscimol or bicuculline-injected mice at any dose. The role of septal GABAergic interneurones in the indirect transsynaptic control over the basal and activated states of septo-hippocampal cholinergic activity is discussed with respect to the concept that these complex neuronal interactions contribute to the physiological mechanisms involved in the modulation of working memory performance.

Muscimol infused into the medial septal area impairs long-term memory but not short-term memory in inhibitory avoidance, water maze place learning and rewarded alternation tasks

These experiments investigated the effects of injections of muscimol (1 or 5 nmol), administered into the medial septal area prior to training, on memory tested at different retention delays after training in 3 tasks: an inhibitory avoidance task, a one-trial place learning task, and a rewarded alternation task. In all 3 tasks, intraseptal injections of muscimol did not impair memory performance at short retention delays, but impaired memory at the longer retention delays. These findings are consistent with the view that GABAergic regulation of the septohippocampal cholinergic system plays a selective role in the establishment of long-term memory.