Interactions between 192-IgG saporin and intraseptal cholinergic and GABAergic drugs: Role of cholinergic medial septal neurons in spatial working memory.

Rats were administered 192-IgG saporin (SAP) or vehicle into the medial septum-vertical limb of the diagonal band (MS-vDB). Starting 1 week later, the effects of intraseptal scopolamine, oxotremorine, and muscimol were tested in a T-maze alternation task. Choice accuracy in the absence of infusions did not differ between control and SAP-treated rats. Intraseptal scopolamine or muscimol impaired the choice accuracy of SAP-treated but not control rats. Oxotremorine impaired accuracy similarly in control and SAP-treated rats. The enhanced effects of scopolamine and muscimol produced by SAP are consistent with the hypothesis that cholinergic MS-vDB neurons are used in spatial working memory. The finding that SAP alone did not alter choice accuracy provides further evidence that cholinergic MS-vDB neurons are not necessary for spatial working memory. Thus, cholinergic MS-vDB neurons are involved in but not necessary for spatial working memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of opioid microinjections into the medial septal area on spatial memory in rats.

Recent work has demonstrated that posttraining systemic opioid antagonist administration facilitates the acquisition of a radial arm maze task in new spatial environments. In this study, we examined the effect of posttraining naloxone and β-endorphin microinjections into the medial septal area on the acquisition of a radial maze task in new spatial environments. The results of these experiments demonstrated that posttraining intraseptal naloxone administration facilitated, whereas posttraining intraseptal β-endorphin administration impaired, the acquisition of criterion performance on a maze task performed in new spatial environments. Further, intraventricular β-endorphin administration did not produce effects that were comparable to those observed following intraseptal β-endorphin administration, which indicates that the septal region is a brain site that is sensitive to the effects of opioids on spatial memory in new environments. Further, posttraining intraseptal β-endorphin administration had no effect on working memory in a familiar spatial environment, whereas pretraining intraseptal β-endorphin administration had no effect on the performance of a previously acquired spatial task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of selective immunotoxic lesions of medial septal cholinergic cells on spatial working and reference memory.

The effect of injection into the medial septum of a toxin selective for cholinergic neurons, 192 IgG-saporin, was examined in rats trained to perform 2 versions of the radial 8-arm maze task. Rats were first trained to perform a task with varying delays (0, 1, 2 min) imposed between the 4th correct arm choice and access to all 8 arms. Lesioned rats made significantly more errors in the first 4 choices compared with controls and significantly more errors after delays; however, this effect was not delay dependent. Rats were then trained on a different version of this 8-arm maze task in which they learned to avoid 2 arms that were never baited. There was no treatment effect on acquisition of this task. These data are consistent with the hypothesis that the cholinergic projection to the hippocampus facilitates the acquisition of information into the system responsible for short-term memory for locations visited (spatial working memory) but is not involved in retention of this information. It also appears to play no role in either the acquisition or retention of place-nonreward associations (spatial reference memory). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cholinergic modulation of the content of temporal memory.

The pharmacological effects of anticholinesterases (physostigmine and neostigmine) and cholinergic receptor blockers (atropine and methylatropine) on the content of temporal memory in the rat were studied with the use of a 20-s peak-interval procedure with auditory signals. Physostigmine administered ip decreased the variability of the temporal discrimination and shifted peak times permanently leftward on the time scale in a dose-dependent fashion (0.01, 0.03, & 0.09 mg/kg). Neostigmine (0.03 mg/kg) did not produce any of these effects. Atropine administered ip increased the variability of the temporal discrimination and shifted peak times permanently rightward on the time scale in a dose-dependent fashion (0.05, 0.15, & 0.45 mg/kg). Methylatropine (0.15 mg/kg) did not produce any of these effects. Application of a scalar timing model indicated that physostigmine decreased the remembered times of reinforcement and increased sensitivity to time, whereas atropine increased the remembered times of reinforcement and decreased sensitivity to time. These results suggest that the effective level of brain acetylcholine sets the communication speed for the translation of durations measured by the internal clock into values stored in temporal memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Posterodorsal septal lesions impair performance on both shift and stay working memory tasks.

Two groups of male Long-Evans rats (N?=?42) were trained preoperatively on either a shift or a stay problem in a T-maze. Training trials consisted of 2 runs, an "information run" in which S was forced to go down 1 of the 2 arms of the T-maze, followed immediately by a "choice run" in which S could choose either arm. In the shift condition, Ss were rewarded with wet mash only for choosing the arm opposite the one they entered on the information run. In the stay condition, Ss were rewarded for entering the arm that was entered on the information run. The shift group reached 100% performance accuracy after fewer trials than the stay group. Choice accuracy in both groups declined as the delay increased and returned to 100% at the 0-sec delay. Half of the Ss in each condition then received either lesions of the posterodorsal septum—aimed at disconnecting the septum and hippocampus—or control surgery. Results indicate that deficits in maze performance by Ss with septo-hippocampal damage were not restricted to tasks that require alternation of spatial locations. This finding falsifies the notion that maze deficits reflect a spontaneous alternation deficit or changed "spatial strategy," but it supports the hypothesis of a working memory deficit in these Ss. (4 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of cytotoxic entorhinal lesions and electrolytic medial septal lesions on the acquisition and retention of a spatial working memory task

This study assesses how social desirability affects responses in clinical self-report inventories. Six hundred items gathered from four normal personality questionnaires were adapted to devise a pre-experimental personality questionnaire (pre-EMHQ). Results obtained from administering Ko's Mental Health Questionnaire (KMHQ) and the pre-EMHQ to separate samples were the proportion of individuals answering "true" to each item (i.e., P(t)) and the social desirability scale value (i.e., SDSV) of each item. The Experimental Mental Health Questionnaire (EMHQ) was established from the pre-EMHQ by closely matching the P(t)s and the SDSVs of the two questionnaires. Administering the KMHQ and the EMHQ concurrently to another sample provided results for factor analysis and other statistical analyses. The SDSVs and the P(t)s for each of the KMHQ items certainly displayed a linearly increasing relation. The two sets of corresponding subscales also correlated significantly. By applying the polynomial regression analysis, the tendency to score might be expressed as a quadratic function of SDSVs. Two iterative principal-factor analyses of the two sets of subscales each resulted in two factors, and Factor 1 is similar in both the KMHQ and the EMHQ. In brief, social desirability plays a critical role in affecting responses in a clinical self-report inventory. The factors involved and suggestions proposed will be of value for further research.     

A comparison between the effects of medial septal lesions and entorhinal cortex lesions on performance of nonspatial working memory tasks and reversal learning

Two studies explored the relationship between cognitions and long-term symptoms in adult child sexual abuse (CSA) survivors. In Study 1, an American sample of 43 survivors completed questionnaires assessing attributional style and dysfunctional beliefs in cognitive themes affected by victimization, as well as measures of posttraumatic symptoms. Survivors' attributions of negative events were more internal, stable, and global than those of 29 comparison subjects without a history of CSA. However, only the globality scale was significantly related with severity of long-term symptoms. High correlations between dysfunctional beliefs concerning safety, trust, esteem, or intimacy, and posttrauma symptoms were found. The latter finding was replicated in Study 2 with a German sample of 35 CSA survivors, even when controlling for frequency of abuse.     

Neuropsychology and working memory: A review.

Reviews the relationship between neuropsychological approaches to human memory and the working memory theory introduced by A. D. Baddeley and G. J. Hitch (1974). It is argued that neuropsychological perspectives have made a number of different contributions to the development of the theory. On occasion, they have provided unique natural experiments that cannot be simulated in the laboratory and that represent a significant input to theoretical refinement. They also yield a rich source of information on a central tenet of working memory theory, which is that the components of working memory support everyday complex cognitive activities. Neuropsychological studies have played an important role in identifying the contributions of the phonological loop to the acquisition and processing of language and of the visuospatial sketchpad to learning to recognize new faces. More generally, neuropsychological investigations have substantially reinforced developments of theory based on work from the experimental laboratory, and they provide convincing evidence for the robustness and generality of the theory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Medial septal lesions disrupt spatial, but not nonspatial, working memory in rats.

In Exp 1, rats with small medial septal lesions were less able than were control rats to remember the location of the arm of a Y maze they had been forced to enter on the preceding sample run. Moreover, as the retention interval between the sample and choice runs on this spatial delayed nonmatching-to-sample (DNMTS) task was increased to 1 and 2 min, the magnitude of the deficit increased. In contrast, these same lesioned rats were not deficient in Exp 2 in their ability to remember the object they had encountered in the straight alley on the sample run. In fact, when the retention interval was increased to 1 min on this nonspatial DNMTS task, the rats with medial septal lesions were more accurate than were the controls. This pattern of results did not appear to be due to task difficulty, recovery of function, or sequence of training. Rather, these results indicate that damage to the septohippocampal system disrupts spatial working memory more than it disrupts nonspatial working memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reversible inactivation of the medial septum or nucleus basalis impairs working memory in rats: a dissociation of memory and performance

Lidocaine-induced inactivation of the medial septum immediately after training or prior to testing in a delay radial-arm maze task produced deficits in spatial working memory that reflected impaired acquisition of the task. Injection of lidocaine into the nucleus basalis magnocellularis produced a profile of behavioral changes that indicated that temporary inactivation of this structure impaired the behavioral expression of information already stored in working memory. This appears to reflect an impairment in processes that are required for performance (i.e., attention, motivation, sensorimotor function) of the task but not for retrieval of stored information. Site-specific inactivation of the basal forebrain should help to reveal the involvement of its component structures in different aspects of cognitive function.     

Cholinergic effects on spatial exploration and its memory

In their first swim in an unfamiliar circular swimming pool, control rats showed declines in average swimming speed and in the time spent in the perimeter of the pool. Both declines were antagonized by the muscarinic antagonist scopolamine, but not by methylscopolamine, a muscarinic antagonist that crosses the blood-brain barrier only poorly, indicating that these declines depend upon central cholinergic activity. In the first minute of a second swim 3 days later, control rats spent a much longer time in the central region of the pool than in the first minute of the first swim. This modification of behaviour by previous experience suggests that a long-term memory of the first swim was formed. Scopolamine, but not methylscopolamine, administered before the first swim attenuated this modification of behaviour. Pilocarpine, administered shortly after scopolamine before the first swim, significantly normalized all the scopolamine-induced changes, whereas oxotremorine and arecoline normalized only habituation of perimeter preference; agonists administered alone decreased swimming speed and perimeter preference without affecting their rates of decline. The results suggest that in this test, different cholinergic mechanisms are involved in habituation of swimming speed and habituation of perimeter preference.     

Effect of low-intensity hippocampal stimulation on spatial versus working memory in rats.

Investigated differing predictions from the spatial mapping hypothesis of hippocampal function proposed by O'Keefe and Nadel (1978) and the working memory hypothesis proposed more recently by Olton and colleagues (Olton, Becker, & Handelmann, 1979). Each of 2 groups of rats was trained to use a different strategy to locate a submerged platform in opaque water. The MAP group used a spatial mapping strategy to reach a platform in a fixed location, whereas the CUE group used a guidance strategy, which involved following a cue that signaled the location of a randomly placed platform. Half of each group was given low-level unilateral electrical stimulation of the dentate gyrus and immediately tested on the water maze task. Results of Exp 1 show that both the MAP and CUE groups were impaired by stimulation. However, there was an inadvertent spatial element involved in the CUE task. When this element was eliminated in Exp 3, the same CUE Ss were unaffected by a 2nd series of stimulation trials, whereas the MAP Ss continued to show impairment. Results strongly support the cognitive mapping hypothesis and provide little support for the working memory hypothesis of hippocampal function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Consequences of selective blockade of septal noradrenergic afferents on anxiety and spatial working memory performance in mice

We have previously reported a high prevalence of endemic renal tubular acidosis (EnRTA) in the northeast of Thailand, and our subsequent studies provided evidence that K deficiency exists in the same region. Since tubulointerstitial damage is associated with K deficiency, we postulate that this might be implicated in the pathogenesis of EnRTA and, if so, that a spectrum of tubulointerstitial abnormalities can be anticipated. In this study we evaluated renal acidification ability in 4 patients and in 11 of their relatives. We used a 3-day acid load (NH4Cl 0.1 g/kg/day) followed by 20 mg oral furosemide and monitored the maximal renal concentrating ability using water deprivation and intranasal 1-deamino-D-arginine vasopressin. The results showed that the subjects could be divided into three groups; normal relatives of the patients, those with suspected renal tubular acidosis, and patients with overt EnRTA who had chronic metabolic acidosis and a low rate of excretion of NH4+. The rate of excretion of K was very low (20 +/- 4 mmol/day) in patients with EnRTA and in their relatives with suspected EnRTA. The transtubular K concentration gradient was also very low in their relatives, especially in patients with suspected EnRTA (2.8 +/- 0.2). With a 3-day NH4Cl load, the rate of excretion of NH4+ was very low in patients with EnRTA (32 +/- 9 mmol/day), and the relatives with suspected EnRTA also had a decreased capacity to excrete NH+4 (50 +/- 14 mmol/day). In contrast, the normal relatives excreted 92 +/- 12 mmol of NH+4/day. The patients with EnRTA could lower their urine pH to less than 5.5 after the acid loading (6.2 +/- 0.3). After furosemide (20 mg), the NH4+ excretion in the patients with EnRTA was lower than in the normal relatives. Moreover, the minimum urine pH in patients with EnRTA did not fall (6.1 +/- 0.2), but there was a fall to 4.8 +/- 0.1 in the patients with suspected EnRTA after furosemide treatment. In conclusion, there was a spectrum of tubulointerstitial abnormalities ranging from suspected to overt distal RTA in a geographic area known to have a high prevalence of K deficiency. K deficiency might be the important pathogenetic factor of EnRTA in the northeast of Thailand.     

The aging of working memory.

Research concerned with relations between adult age and working memory is reviewed, especially that relevant to the A. D. Baddeley (e.g., see PA, Vol 79:26150; see also Baddeley & G. J. Hitch, 1974) model of working memory. The evidence suggests that although increased age is associated with lower scores on measures of working memory functioning, many of the age-related influences appear to be mediated by a slower speed of processing. Furthermore, recent studies indicate that slower processing primarily influences the time required to achieve a stable encoding of the information rather than the rate at which information is lost across time or subsequent processing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impact of working memory training on memory performance in old-old adults.

Memory impairments constitute an increasing objective and subjective problem with advancing age. The aim of the present study was to investigate the impact of working memory training on memory performance. The authors trained a sample of 80-year-old adults twice weekly over a time period of 3 months. Participants were tested on 4 different memory measures before, immediately after, and 1 year after training completion. The authors found overall increased memory performance in the experimental group compared to an active control group immediately after training completion. This increase was especially pronounced in visual working memory performance and, to a smaller degree, also in visual episodic memory. No group differences were found 1 year after training completion. The results indicate that even in old?old adults, brain plasticity is strong enough to result in transfer effects, that is, performance increases in tasks that were not trained during the intervention. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impulsive decision making and working memory.

Decision making that favors short-term over long-term consequences of action, defined as impulsive or temporally myopic, may be related to individual differences in the executive functions of working memory (WM). In the first 2 experiments, participants made delay discounting (DD) judgments under different WM load conditions. In a 3rd experiment, participants high or low on standardized measures of impulsiveness and dysexecutive function were asked to make DD judgments. A final experiment examined WM load effects on DD when monetary rewards were real rather than hypothetical. The results showed that higher WM load led to greater discounting of delayed monetary rewards. Further, a strong direct relation was found between measures of impulsiveness, dysexecutive function, and discounting of delayed rewards. Thus, limits on WM function, either intrinsic or extrinsic, are predictive of a more impulsive decision-making style. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of manipulation and irrelevant noise on working memory capacity of patients with Alzheimer's dementia.

The effect of manipulation and distracting noise on immediate serial recall was measured in patients with dementia of the Alzheimer type (DAT), neurologically healthy elderly individuals, and young adults. In Experiment 1, the authors compared serial word recall with word recall in alphabetical order. Alphabetical recall requires the active manipulation of the contents of working memory. Findings indicated that DAT patients were severely impaired in the alphabetical recall task, whereas the performance of neurologically healthy elderly participants was comparable with the performance of young adult participants. In Experiment 2, the authors investigated the effect of different irrelevant auditory backgrounds on immediate digit recall. In this task, both elderly participants and DAT patients performed similarly to the group of young adult participants, indicating comparable efficacy to resist auditory distraction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cholinergic blockade, septal lesions, and DRL performance in the rat.

Reports 4 experiments with a total of 20 male Long-Evans hooded rats describing the effects of cholinergic blockade produced by systemic injection of either atropine sulfate or atropine methyl nitrate on Ss' differential reinforcement of low rate (DRL) responding. It was shown that atropine sulfate injected either chronically or at high dosages suppressed DRL responding. Injected acutely, atropine sulfate produced disinhibitory effects. When atropine was injected either chronically or acutely into Ss with septal lesions, there was suppression of responding. It is suggested that the specific behavioral outcome resulting from cholinergic blockade depends on the balance resulting from the competing peripheral and central effects of such blockade. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of alcohol on working memory: Distinguishing multiple processes.

The authors assessed effects of alcohol consumption on different types of working memory (WM) tasks in an attempt to characterize the nature of alcohol effects on cognition. The WM tasks varied in 2 properties of materials to be retained in a 2-stimulus comparison procedure. Conditions included (a) spatial arrays of colors, (b) temporal sequences of colors, (c) spatial arrays of spoken digits, and (d) temporal sequences of spoken digits. Alcohol consumption impaired memory for auditory and visual sequences but not memory for simultaneous arrays of auditory or visual stimuli. These results suggest that processes needed to encode and maintain stimulus sequences, such as rehearsal, are more sensitive to alcohol intoxication than other WM mechanisms needed to maintain multiple concurrent items, such as focusing attention on them. These findings help to resolve disparate findings from prior research on alcohol's effect on WM and on divided attention. The results suggest that moderate doses of alcohol impair WM by affecting certain mnemonic strategies and executive processes rather than by shrinking the basic holding capacity of WM. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of septal area damage and base-line activity levels on conditioned heart-rate response in rats.

Exp. I subjected 7 unrestrained male Long-Evans rats with septal area lesions and 8 nonoperated controls to Pavlovian heart-rate conditioning with footshock as the UCS. Experimental Ss displayed lower degrees of tachycardia to both the CS and UCS than did controls, but there were no significant differences in amount of skeletal movement. In Exp. II, 6 control and 6 septal-damaged Ss received CS-shock pairings while lever pressing for food and while not lever pressing. There was no difference in conditioned suppression, but less conditioned tachycardia was again seen in experimental Ss, indicating dissociation between the 2 measures of conditioning. All Ss exhibited greater tachycardia during the non-lever-pressing condition, illustrating the effect of base-line activity on conditioned heart-rate responses. (24 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)