Choline-induced spatial memory facilitation correlates with altered distribution and morphology of septal neurons.
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Animals↗
Biomedical subjects
W H Meck
Publications and source records attributed to W H Meck.
The organizational effects of gonadal steroids on sexually dimorphic spatial ability.
Numerous studies have provided evidence that both human and nonhuman males reliably outperform females on tasks that require spatial ability. Because most of the research on this topic has utilized hormonally normal adults as subjects, it is still not known to what extent, if any, sex differences in spatial ability can be attributed to hormonally organized dimorphisms in neural structures subserving cognitive function. The purpose of this paper is to address this critical issue in three areas: (1) Research that demonstrates that male rodents initially outperform females on maze tasks that utilize visuospatial representation will be reviewed. (2) New data which provide strong evidence for the organizational effects of gonadal steroids will be described. The timing of the sensitive period for hormone action, the specific hormones involved and their possible sites of action will be discussed. (3) The question of what behavioral processes hormones might be affecting to cause differential performance on spatial tasks will be examined. The studies described in this review suggest that gonadal steroids, probably the testosterone metabolite estradiol, cause organizational effects during perinatal development which have multiple effects on the associational-perceptual-motor biases that guide visuospatial navigation.
Animals↗
Organizational effects of early gonadal secretions on sexual differentiation in spatial memory.
Neonatally castrated (MNC) and control male rats (MC) and female rats treated neonatally with estradiol benzoate (FNE) and female controls (FC) were studied. In Exp. 1 spatial memory was assessed using a 12-arm radial maze. During acquisition, MC and FNE groups were more accurate in choice behavior than FC and MNC groups. In Exp. 2 the discriminative control exerted by different types of cues was evaluated. Alteration of the geometry of the room but not movable landmarks disrupted performance of MC and FNE groups. For the FC and MNC groups, alteration of either geometry or landmarks did not disrupt performance. In Exp. 3 the effect of a 15-min delay was determined. MC and FNE groups were more disrupted by a delay than MNC and FC groups. Together, these data suggest that early exposure to gonadal steroids (probably estradiol) improves acquisition of spatial tasks by reorganizing and simplifying associational-perceptual processes that guide spatial ability.
Animals↗
Hierarchical structures: chunking by food type facilitates spatial memory.
Three experiments assessed the ability of male Sprague-Dawley rats to organize the spatial locations of different food types in a hierarchical manner to maximize the efficiency of working memory. Independent groups were exposed, on a 12-arm radial maze, to baiting arrangements varying in the stability of the pattern and type of food used as bait. Training rats with stable, differentiable baiting arrangements produced increased accuracy in choice performance, hierarchically ordered patterns of choice selection, slower growth of proactive interference when trials were massed, and the learning of the geometrical relations among food types independent of other extramaze cues. Such findings are strong evidence of the rat's ability to encode and use local cues for navigation, based on properties of the reinforcer. The application of a chunking strategy may provide for more efficient use of working memory by facilitating information storage, recall, or resetting mechanisms.
Animals↗
Organizational changes in cholinergic activity and enhanced visuospatial memory as a function of choline administered prenatally or postnatally or both.
This experiment was an examination of the effects of supplemental dietary choline chloride given prenatally (to the diet of pregnant rats) and postnatally (intubed directly into the stomachs of rat pups) on memory function and neurochemical measures of brain cholinergic activity of male albino rats when they became adults. The data demonstrate that perinatal choline supplementation causes (a) long-term facilitative effects on working and reference memory components of a 12-arm radial maze task, and (b) alternations of muscarinic receptor density as indexed by [3H]quinuclidinyl benzilate (QNB) binding and choline acetyltransferase (ChAT) levels in the hippocampus and frontal cortex of adult rats. An analysis of the relationship between these organizational changes in brain and memory function indicated that the ChAT-to-QNB ratio in the hippocampus is highly correlated with working memory errors, and this ratio in the frontal cortex is highly correlated with reference memory errors.
Age Factors↗
Pre- and postnatal choline supplementation produces long-term facilitation of spatial memory.
Although research has demonstrated that short-term improvement in memory function of adult rats can occur when the availability of precursors for the neurotransmitter acetylcholine is increased, little is known about whether memory function of adult rats can be permanently altered by precursor supplementation during early development. In the present study, male albino rats were exposed to choline chloride supplementation both prenatally (through the diet of pregnant rats) and postnatally (subcutaneous injections). At 60 days of age rats were tested on a 12- and 18-arm radial maze task. Results indicated that compared to control littermates, perinatal choline-treated rats showed more accurate performance on both working and reference memory components of the task. This performance difference was apparent on the first block of sessions and continued throughout training. Further analysis revealed that the difference between choline and control rats is not due to use of differential response or cue-use strategies. Instead, it appears that choline induced performance differences are due to long-term enhancement of spatial memory capacity and precision.
Animals↗
Attention and the frontal cortex as examined by simultaneous temporal processing.
The brain mechanisms involved in attention and memory were examined by testing rats in temporal discriminations designed to emphasize these cognitive processes. Normal rats were able to time each of two stimuli whether they were presented alone or together. Rats with lesions of the frontal cortex (FC) or nucleus basalis magnocellularis (NBM) were able to time each stimulus when it was presented alone, but not when it was presented together with another stimulus. Rather, these rats timed only the intruding stimulus and ignored the other, demonstrating a failure of divided attention. Rats with lesions of the fimbria-fornix (FF) or medial septal area (MSA) performed the divided attention task normally, but failed to remember the duration of a stimulus that had been terminated temporarily earlier in the trial, demonstrating a failure of working memory. These results provide another informative dissociation between the functions of the frontal and hippocampal systems, emphasizing frontal involvement in attention, and hippocampal involvement in working memory.
Animals↗
Hippocampal function is required for feedback control of an internal clock's criterion.
A discrete-trial peak-interval procedure was used to evaluate the effects of hippocampal damage on the control of an internal clock's criterion. Rats first received either lesions of the fimbria-fornix or sham operations. Following surgery rats were trained on a 20-s peak-interval procedure and later were transferred to a 10-s peak-interval procedure. Rats with sham operations were maximally responsive about the time that reinforcement was sometimes made available (10 or 20 s) and showed an oscillation of successive peak-time values similar to biological feedback control systems. In contrast, rats with fimbria-fornix lesions were maximally responsive at a time about 20% earlier than the time that reinforcement was made available (8 or 16 s) and showed no control of successive peak-time values. Taken together, these results demonstrate that a fimbria-fornix lesion reduces the remembered time of reinforcement stored in reference memory, interferes with the internal control of temporal criteria stored in working memory, and has no effect on the animal's sensitivity to stimulus duration or the acquisition of a new temporal criterion.
Animals↗
Separation of hippocampal and amygdaloid involvement in temporal memory dysfunctions.
The role of the hippocampus and the amygdala in timing and in the memory of previously timed events was investigated in rats. Two testing procedures used the peak time (the time at which the maximum response rate occurred) to identify the time at which the rat expected reinforcement. Amygdala (AMG) lesions had no effect on the remembered time of reinforcement or on the ability to remember the duration of a previous stimulus. Fimbria-fornix (FF) lesions had two effects: these rats remembered the time of reinforcement as occurring earlier than it really did, and could not remember the duration of a previous stimulus even after a gap of only 0.5 s. This behavior pattern endured throughout testing in spite of reinforcement contingencies designed to eliminate it. Atropine, 0.45 mg/kg, caused control rats to forget the duration of a previous stimulus, while haloperidol, 0.15 mg/kg, did not. Taken together, these data indicate that the hippocampus, but not the amygdala, has an important role in the memory for time. They suggest that alterations in temporal processes may be intimately involved in the amnesic syndrome seen following damage to temporal lobe structures.
Amygdala↗
Vasopressin metabolite neuropeptide facilitates simultaneous temporal processing.
Rats were trained on a peak-interval timing procedure in which auditory, tactile, and visual stimuli signaled 3 different fixed-interval schedules (15, 30, and 60 s) that were presented simultaneously in a hierarchical fashion. Administration of vasopressin metabolite neuropeptide [pGlu-Asn-Cys(Cys)-Pro-Arg-Gly-NH2, 0.3 microgram/kg i.p.] had two main effects on performance. With repeated exposure the temporal criterion for each of the intervals shifted leftward on the time scale in a proportional manner, and the probability of attention to each of the intervals increased proportionally. The conclusion is that vasopressin metabolite neuropeptide facilitates simultaneous temporal processing by increasing the speed of mental processes involved in memory storage and divided attention. These results indicate that a major metabolite of arginine vasopressin that is devoid of endocrine and pressor activity can produce facilitation of cognitive processes in animals.
Animals↗
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.
Animals↗
Nutrients that modify the speed of internal clock and memory storage processes.
Two experiments assessed the effects of nutrients on timing behavior by rats. The nutrients were laced with saccharin and given to rats as a snack before training on a 20-s peak-interval procedure. The primary component of the snacks for four groups of 10 rats was lecithin (phosphatidylcholine), protein (casein), carbohydrate (sucrose), or a nonnutrient (saccharin). The primary measure of behavior was the time of the rat's highest response rate during a trial (peak time), which represented the interval during which the rat maximally expected food. With a lecithin snack, peak time was gradually shifted over sessions to a shorter time, remained shifted to the left of the normal function with additional testing, and then remained at the shorter time on two sessions after the snack was discontinued; with the protein snack, peak time was abruptly shifted to a shorter time, returned to normal with additional testing, and then rebounded to a longer time when the snack was discontinued; with a carbohydrate, snack peak time was abruptly shifted to a longer time, returned to normal with additional testing, and then rebounded to a shorter time when the snack was discontinued. The behavioral patterns produced by the nutrients were interpreted in terms of precursor effects on central neurotransmitter synthesis and release, psychological stages of an information-processing model, and mathematical parameters of a scalar timing theory.
Animals↗
Nucleus basalis magnocellularis and medial septal area lesions differentially impair temporal memory.
Functional dissociations between the medial septal area (MSA) and the nucleus basalis magnocellularis (NBM) were examined using the concepts and experimental procedures developed by scalar timing theory. Rats were tested in variations of a signalled discrete-trial peak-interval schedule of reinforcement in which the response rate functions identified the time when the rats expected reinforcement. The variations assessed aspects of both reference and working memory for information obtained from prior trials and from the current trial. A double dissociation was found in reference memory. Rats with NBM lesions, like those with frontal cortex (FC) lesions, remembered the time of reinforcement as having occurred later than it actually did; rats with MSA lesions, like those with fimbria-fornix (FF) lesions, remembered the time of reinforcement as having occurred earlier than it did. A single dissociation was found in working memory. MSA lesions and FF lesions impaired working memory, while NBM and FC lesions had no effect on it. These data begin to identify the brain mechanisms underlying temporal memory; they indicate that the frontal and hippocampal systems are both involved, but in complementary ways; and they provide information that helps specify more clearly the functions of the frontal and hippocampal systems.
Animals↗
Arginine vasopressin innoculates against age-related increases in sodium-dependent high affinity choline uptake and discrepancies in the content of temporal memory.
Systemic injections of arginine vasopressin (AVP, 0.08 pressor units/kg i.p.) to mature rats (10-13 months) trained on a positively reinforced timing task prevented the age-related discrepancies in the content of temporal memory and the increases in sodium-dependent high affinity choline uptake (SDHCU) in the frontal cortex observed in control rats when the rats became aged (27-30 months). AVP administration had no effect on muscarinic receptor density as measured by [3H]quinuclidinyl benzilate (QNB) binding or on choline acetyltransferase (ChAT) levels in either the hippocampus or the frontal cortex.
Aging↗
Affinity for the dopamine D2 receptor predicts neuroleptic potency in decreasing the speed of an internal clock.
For each of five neuroleptics (chlorpromazine, haloperidol, pimozide, promazine, and spiroperidol), the dose required to produce a rightward horizontal shift of 15-20% for psychophysical bisection functions that relate the percentage of long responses to signal duration was determined in rats for two different signal ranges (2-8 sec and 4-16 sec). Affinity for the dopamine D2 receptor (from in vitro studies) predicted neuroleptic potency in producing the criterion shift of the timing functions, whereas affinity for other aminergic receptors (D1, D3, the alpha-noradrenergic receptor, S1, and S2) did not. The conclusion is that dopamine D2 receptors play a major role in determining the rate of temporal integration for time estimation.
Animals↗
Postreinforcement signal processing.
Postreinforcement signal processing by rats was demonstrated in six experiments that used a discrete-trials choice procedure. Experiment 1 assessed the extent to which rats are able to transfer knowledge about associations between postreinforcement signal durations and choice responses to conditions where a particular signal duration preceded the opportunity to make a choice response. In Experiment 2 the generality of the transfer effect was demonstrated by using both signal duration and signal modality as relevant stimulus attributes for the postreinforcement signals. The role of the relative durations of the reinforcement-signal gap and the intertrial interval was investigated in Experiment 3. In order to assess the effects of within-trial and between-trial signal relations on the acquisition of a temporal discrimination, both pre-and postreinforcement signals were presented on each trial in Experiments 4 and 5. The effects of pre- and postreinforcement signal relations on the steady-state performance of a temporal bisection task across three different signal ranges were studied in Experiment 6. The conclusion is that rats readily process various stimulus attributes of postreinforcement signals and that relations between postreinforcement signals, choice responses, and prereinforcement signals are major determinants of choice behavior.
Animals↗
Arginine vasopressin inoculates against age-related changes in temporal memory.
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Acetylcholine↗
Temporal integration in duration and number discrimination.
Temporal integration in duration and number discrimination by rats was investigated with the use of a psychophysical choice procedure. A response on one lever ("short" response) following a 1-s white-noise signal was followed by food reinforcement, and a response on the other lever ("long" response) following a 2-s white-noise signal was also followed by food reinforcement. Either response following a signal of one of five intermediate durations was unreinforced. This led to a psychophysical function in which the probability of a long response was related to signal duration in an ogival manner. On 2 test days, a white-noise signal with 5, 6, 7, 8, or 10 segments of either 0.5-s on and 0.5-s off or 1-s on and 1-s off was presented, and a choice response following these signals was unreinforced. The probability of a long response was the same function of a segmented signal and a continuous signal if each segment was considered equivalent to 200 ms. A quantitative fit of a scalar estimation theory suggested that the latencies to initiate temporal integration and to terminate the process are both about 200 ms, and that the same internal accumulation process can be used for counting and timing.
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