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PubMed2004

Spatially directed movement and neuronal activity in freely moving monkey.

The abilities to plan a series of movements and to navigate within the environment require the functions of the frontal and ventromedial temporal lobes, respectively. Neuropsychological studies posit the existence of egocentric (prefrontal) and allocentric (ventromedial temporal) spatial frames of reference that mediate these functions. To examine neural mechanisms underlying egocentric and allocentric guidance of movement, we have developed behavioral and neurophysiological techniques for freely moving monkey. In this chapter, we provide evidence that the dorsolateral prefrontal cortex is important for egocentric spatial tasks in both the visual and tactile modalities, but it does not contribute to performance of an allocentric spatial task. Moreover, neurophysiological recordings indicate that prefrontal neurons are involved in monitoring the spatial nature of behavioral sequences in an egocentric memory task. In contrast, hippocampal neurons are active during spatially directed locomotion, apparently reflecting the monkey's location in a testing room. This discharge is independent of the task's contingencies.

Animals↗
PubMed2006

Dynamics of emotional effects on spatial attention in the human visual cortex.

An efficient detection of threat is crucial for survival and requires an appropriate allocation of attentional resources toward the location of potential danger. Recent neuroimaging studies have begun to uncover the brain machinery underlying the reflexive prioritization of spatial attention to locations of threat-related stimuli. Here, we review functional brain imaging experiments using event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI) in a dot-probe paradigm with emotional face cues, in which we investigated the spatio-temporal dynamics of attentional orienting to a visual target when the latter is preceded by either a fearful or happy face, at the same (valid) location or at a different (invalid) location in visual periphery. ERP results indicate that fearful faces can bias spatial attention toward threat-related location, and enhance the amplitude of the early exogenous visual P1 activity generated within the extrastriate cortex in response to a target following a valid rather than invalid fearful face. Furthermore, this gain control mechanism in extrastriate cortex (at 130-150 ms) is preceded by an earlier modulation of activity in posterior parietal regions (at 40-80 ms) that may provide a critical source of top-down signals on visual cortex. Happy faces produced no modulation of ERPs in extrastriate and parietal cortex. fMRI data also show increased responses in the occipital visual cortex for valid relative to invalid targets following fearful faces, but in addition reveal significant decreases in intraparietal cortex and increases in orbitofrontal cortex when targets are preceded by an invalid fearful face, suggesting that negative emotional stimuli may not only draw but also hold spatial attention more strongly than neutral or positive stimuli. These data confirm that threat may act as a powerful exogenous cue and trigger reflexive shifts in spatial attention toward its location, through a rapid temporal sequence of neural events in parietal and temporo-occipital areas, with dissociable neural substrates for engagement benefits in attention affecting activity in extrastriate occipital areas and increased disengagement costs affecting intraparietal cortex. These brain-imaging results reveal how emotional signals related to threat can play an important role in modulating spatial attention to afford flexible perception and action.

Attention↗
PubMed2002

Use of the Numerov method to improve the accuracy of the spatial discretisation in finite-difference electrochemical kinetic simulations.

The fourth order accuracy of the spatial discretisation of time-dependent reaction-diffusion equations, in finite-difference electrochemical kinetic simulations in one space dimension, might well be achieved by means of the three-point Numerov method, instead of the 5(6)-point discretisation of second spatial derivatives, recently suggested in the literature. This is proven theoretically, and tested in simulations of potential-step chronoamperometric and current-step chronopotentiometric transients for the Reinert-Berg system, which is a classical example of electrochemical reaction-diffusion equations. Although less generally applicable than the 5(6)-point spatial scheme, the Numerov discretisation is easier to use, because it does not lead to increased linear equation matrix bandwidth, but results in quasi-block-tridiagonal matrices, similar to those for the conventional, second order accurate, three-point spatial discretisation. The simulations reveal that the Numerov method brings an improvement of accuracy and efficiency that is comparable with the one offered by the 5(6)-point spatial scheme.

Journal Article↗
PubMed1994

The spatial distribution and geographic analysis of endodontic office locations at the national scale.

The major purpose of this article was to quantify and describe the spatial distribution of endodontic office locations at the national scale. This study consisted of 2858 US American Association of Endodontists member endodontists as subjects. Three research questions were developed and explored. The location quotient technique, the spatial autocorrelation approach, and the multiple-regression procedure were the major analytical methods. Major results were as follows: the highest concentration (2.09 to 2.62) of endodontic offices per 100,000 US population was located in just two states, Massachusetts and Connecticut; the spatial distribution of endodontic office locations did exhibit significant (p < or = 0.05, two-tailed test) spatial autocorrelation. Therefore, the spatial distribution of endodontic office locations was nonrandom. Individually, the most significant predictor of endodontic office locations was the location of general practice dentists (its beta coefficient was 0.960606, significant at p < or = 0.0001).

Adult↗
PubMed1985

Effects of opiate antagonists on spatial memory in young and aged rats.

The effects of post-training opiate antagonist administration on spatial memory were assessed in young and aged male Long Evans rats. In Experiment I rats were trained to visit each arm of an eight-arm radial maze once in a session to obtain a food reward placed at the end of each arm. During training aged rats required significantly more trials to achieve criterion performance when compared to young mature rats. However, administration of the opiate antagonist naloxone (2.0 mg/kg) immediately after each training trial did not significantly alter the rate of achieving accurate performance in either age group. In Experiment II young and aged rats that were previously trained to a comparable criterion on the radial maze were tested on the same maze apparatus in novel spatial environments. When animals were exposed to novel spatial information, the effects of post-trial opiate antagonists were examined using a within-subjects counter-balanced design. In Experiment IIa naloxone (2 mg/kg) enhanced the performance of both young and aged rats. In Experiment IIB naltrexone (1.0 mg/kg) was found to have a comparable effect of enhancing the performance of both age groups. In addition, in Experiment IIb a significant age-related deficit was found in rats tested in novel spatial environments. These results indicate that opiate antagonists are capable of improving memory for new spatial information in both young and aged rats on a task that is sensitive to behavioral deficits during normal aging.

Age Factors↗
PubMed2000

Postnatal intracerebroventricular administrations of NGF alter spatial memory in adulthood.

The present work assessed the effects of intracerebroventricular injections (2x5 mg/2.5 ml) of recombined human nerve growth factor (rhNGF) at postnatal days 2 and 3 upon the development of spatial learning capacities in rats. The treated rats were trained at the age of 22 days to escape onto an invisible platform at a fixed position in space in a Morris navigation task. For half of the subjects, the training position was also cued, a procedure aimed at facilitating escape and reducing attention to the distant spatial cues. At the age of 2 months all the rats were retrained in the same task. Treatment effects were found in both immature and adult rats. The injection of NGF induced a slight alteration of the immature rats' performance. In contrast, a marked impairment of spatial abilities was shown in the 2-month-old rats. The most consistent effects were a significant increase in the escape latency and a decrease bias towards the training platform area during probe trials. The reduction of spatial memory was particularly marked if the subjects had been trained in a cued condition. Taken together, these experiments reveal that an acute pharmacological treatment that leads to transient modifications during early development might induce a behavioural change long after treatment. Thus, the development and the maintenance of an accurate spatial representation are tightly related to the development of brain structures that could be altered by precocious NGF administrations.

Aging↗
PubMed2001

Effects of medial and dorsal cortex lesions on spatial memory in lizards.

In mammals and birds, the hippocampus is a major learning and memory center that plays a prominent role in spatial memory, the use of distal cues to guide navigation. The role of reptilian hippocampal homologues, the medial and dorsal cortex, in spatial memory has not been thoroughly investigated. The medial and dorsal cortex of reptiles is known to play a role in learning both tasks that are hippocampally dependent and tasks that are not hippocampally dependent in mammals and birds. In order to examine the specific role of the medial and dorsal cortex in spatial memory, we trained medial cortex, dorsal cortex, and sham lesioned Cnemidophorus inornatus lizards to locate the one heated rock of four identical rocks spaced evenly around the perimeter of a circular, sand filled, arena in a cool room. We used probe trials to examine the strategies used by lizards to locate the goal. Medial cortex lesions and dorsal cortex lesions slowed acquisition and altered the strategies used to locate the goal. However, none of the lizards adopted a spatial strategy to locate the goal suggesting that the dorsal cortex and medial cortex are involved in using non-spatial strategies for navigation.

Animals↗
PubMed2002

Impaired metabolic capacity in the perirhinal and posterior parietal cortex lead to dissociation between attentional, motivational and spatial components of exploration in the Naples High-Excitability rat.

This study aimed at investigating the neural substrates of spatial and non-spatial Behavioural components of exploration to novelty by a neurogenetic approach. Thus, functional imaging and Behavioural analysis were carried out in the Naples High-Excitability (NHE) rats, a model of hyperactivity and attention-deficit. Quantitative cytochrome oxidase (C.O.) histochemistry was used to measure the basal metabolic capacity of different forebrain structures. In parallel experiments, exploration in an 8-arm radial maze (Olton-maze) with extra-maze cues was used to measure attentional, motivational and spatial components of Behaviour after feeding rats' ad-libitum or at a reduced diet. Functional imaging analysis: brains from naive rats were stained for quantitative C.O. histochemistry along with standards. NHE rats showed lower C.O. activity in perirhinal and posterior-parietal cortex (all layers) and cortical amygdala, and greater activity in entorhinal cortex (superficial layers). The outer granular cell layer of the dentate gyrus had greater activity in NHE. Behavioural analysis: at low and high motivational level, maze exploration was reinforced during shaping throughout and then only a single arm. The Behaviour was monitored by a CCD camera and videotaped. (i) There was no line difference in working memory during non reinforced maze exploration, independent of the motivational level; (ii) during shaping with all baited arms, there was no line difference in working memory, but NHE rats showed a very low or lower food consumption at low and high motivational level, respectively; (iii) rats showed a higher working memory in finding the single baited arm at high motivational level; (iv) NHE rats paid little attention towards reinforcement upon visiting the baited arm only at low motivational level. Thus, Behavioural and functional neuroimaging analysis suggests the neural substrates of spatial and non-spatial components of exploration to be underlined by different network operations in the neocortical and limbic cortices in the NHE rat lines. Therefore, they appear as an useful tool to the understanding of Attention-Deficit Hyperactivity Disorder (ADHD) in children.

Animals↗
PubMed2002

CREB phosphorylation as a molecular marker of memory processing in the hippocampus for spatial learning.

Regulation of gene transcription via the cyclic adenosine 3',5'-monophosphate (cAMP)-mediated second messenger pathway has been implicated in learning and memory. Although the cAMP response element-binding protein (CREB) is an important transcription factor involved in long-term memory, it remains to be determined whether the CREB-dependent events are attributed to spatial learning and memory in a radial arm maze. Here we demonstrate that cAMP-dependent protein kinase A (PKA) and CREB are activated in the course of spatial learning. The radial maze training in rats resulted in a significant increase in PKA and CREB phosphorylation in the hippocampus in the course of spatial learning, which was followed by spatial memory formation. On the other hand, neither the phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and extracellular signal-regulated kinase (ERK) nor the mRNA level of brain-derived neurotrophic factor was significantly affected. These results suggest that activation of the PKA/CREB signaling pathway in the hippocampus plays an important role in spatial memory formation.

Animals↗
PubMed2003

Spatial memory performance of freely-moving squirrel monkeys.

Few experiments have addressed the problem of cognitive map formation in non-human primates. Therefore, a paradigm was developed to assess spatial memory formation in squirrel monkeys (Saimiri sciureus) moving freely in three dimensions. While moving on the walls and floor of a large test chamber, the animals learned to collect pieces of cereal from baited food-ports interspersed among non-baited ports. The cereal-pellets were not visible to the monkeys, so the animals needed to develop spatial memory to visit only the baited ports for food and avoid the non-baited ones. A session consisted of ten consecutive trials, and 3 successive sessions were conducted on each day for a 5-day period. For each trial, correct choices (CC; number of visited baited-ports) and incorrect choices (IC; number of visited non-baited ports) were registered, and spatial memory performance index (SMPI; ranging from 0.00 to 1.00) was calculated as follows: SMPI=(CC-IC)/CC. For each session, mean SMPI, session duration, total reaches into the non-baited ports, and total reaches into the baited ports were documented. In an 8-port task, where 4 food-ports were baited and 4 were non-baited, the mean SMPI was higher than 0 in the first session (day 1), indicating the development of short-term spatial memory. By the fifth session (day 2), this index was significantly higher than in the first session, indicating the build-up of long-term spatial memory. These changes were related to a significant decrease in the total reaches into the non-baited ports. At the same time, the duration of the sessions and the total reaches into the baited ports did not change significantly. This paradigm can be used for (1) studying cognitive map formation in primates, (2) examining the underlying cellular and molecular mechanisms in integrative neurobiological experiments, and (3) screening cognition-enhancer drugs in a monkey model.

Analysis of Variance↗
PubMed1992

Spatial deficits and hemispheric asymmetries in the rat following unilateral and bilateral lesions of posterior parietal or medial agranular cortex.

Studies of spatial behavior in both the human and non-human primate have generally focused on the role of the posterior parietal and prefrontal cortices and have indicated that destruction of these regions produce allocentric and egocentric deficits, respectively. The present study examined the role of the rodent analogs of these regions, the posterior parietal (PPC) and medial agranular (AGm) cortices, in egocentric and allocentric spatial processing, and whether spatial processing in rodents is organized in a hemispatial and/or lateralized manner as has been found in the primate. Eighty male rats receiving either a unilateral or bilateral lesion of AGm or PPC were examined on an egocentric (adjacent arm) or an allocentric (cheeseboard) maze task. The results indicated that PPC and AGm have dissociable spatial functions. Bilateral AGm destruction resulted in egocentric spatial deficits, and unilateral AGm operates demonstrated an intermediate deficit. In contrast, bilateral PPC operates demonstrated a severe deficit in allocentric processing. In addition, there were lateralized differences in the performance of unilateral PPC operates. While right PPC lesions resulted in a significant deficit on the allocentric task, no such deficit was seen in left PPC operates. In addition, neither unilateral AGm nor unilateral PPC operates demonstrated a hemispatial impairment on either the egocentric or allocentric tasks.

Animals↗
PubMed1996

L-AP4 (L-(+)-2-amino-4-phosphonobutyric acid) induced impairment of spatial learning in the rat is antagonized by MAP4 ((S)-2-amino-2-methyl-4-phosphonobutanoic acid).

L-AP4, an agonist at the metabotrophic glutamate receptors 4, 6, 7, 8 and 9 produced a selective spatial learning impairment in a water maze as well as in an 8-arm maze task when injected i.c.v. (5 microliters of a 80 mM solution), a dose previously reported to block consolidation of long-term potentiation in vivo. Acquisition and recall of the spatial water-maze task, as measured by escape latency and quadrant bias, respectively, were impaired, whereas swim speed was not affected. In contrast, ability to perform a non-spatial control task was not impaired; latency to reach a visible escape platform was not delayed in L-AP4-treated animals. No behavioral difference was visible in the open field. MAP4, an antagonist of mGluRs mediating L-AP4 induced reduction of transmitter release, when administered pretraining i.c.v. (5 microliters of an 80 mM solution) did not affect motor activity in the open field test but did impair learning of both spatial tasks. In addition, swim speed was increased. However, injecting L-AP4 and MAP4 in combination at equimolar concentrations had no effect on learning in both spatial tasks or on swim speed in the water maze. Neither latency in the visible-platform test nor behavior in the open field was affected. We conclude that L-AP4 sensitive metabotropic glutamate receptors play a selective role in learning and memory formation of the rat.

Aminobutyrates↗
PubMed1996

Differential effects of lidocaine infusions into the ventral CA1/subiculum or the nucleus accumbens on the acquisition and retention of spatial information.

Reversible, lidocaine-induced lesions of the CA1/subicular subfield of the ventral hippocampus or the shell region of the nucleus accumbens (N.Acc.) were used to assess the roles of these structure during the acquisition and retention of a spatial response as measured by the Morris water-maze task. Acquisition and retention tests were administered over 2 phases of 6 trials, respectively. Rats receiving reversible lesions of the ventral CA1/subiculum prior to the acquisition phase of this task required significantly longer path lengths to find a hidden platform than animals which received control infusions of artificial cerebrospinal fluid. Rats with similar lesions to the N.Acc. were unimpaired. During the retention phase, 30 min after the acquisition phase, rats with prior ventral CA1/subiculum or N.Acc. lesions had similar path lengths to control animals. Lidocaine infusions into either the ventral CA1/subiculum or N.Acc. prior to the retention phase did not impair performance relative to control animals. These results suggest that the N.Acc. is not involved in either the acquisition or retention of spatial information. In contrast, the ventral CA1/subiculum does appear to be involved in the initial use of novel spatial information necessary for the performance of a spatially mediated escape response, but is not involved in the retention or retrieval of previously acquired spatial information.

Anesthetics, Local↗
PubMed1997

Delay-period activity in the primate prefrontal cortex encoding multiple spatial positions and their order of presentation.

To investigate whether prefrontal neurons temporarily retain information regarding multiple spatial positions, single-neuron activity was recorded while monkeys performed a delayed sequential reaching task, in which they needed to remember two cue positions out of three and their temporal order of presentation. Most neurons were also tested on a conventional delayed reaching task, in which they needed to remember one cue position during the delay. Among 72 neurons that exhibited significant delay-period activity, one group of neurons (n = 19) exhibited delay-period activity only when a visual cue was presented at one of the three positions (position-dependent). Of these, 6 neurons exhibited this activity when a cue was presented at that position independent of the temporal order, whereas 13 neurons exhibited this activity only when a cue was presented at that position in a particular temporal order (e.g., as the first cue or the second cue). Another group of neurons (n = 39) exhibited delay-period activity only when visual cues were presented at two positions out of three (pair-dependent). Of these, 7 neurons exhibited pair-dependent activity independent of the temporal order of cue presentation. However, 32 neurons exhibited this activity only when two cues were presented in a particular temporal order. The remaining 11 neurons exhibited non-differential activity during the delay period and 3 neurons exhibited miscellaneous activity. These results show that a single prefrontal neuron can retain information regarding two spatial positions, and that, to retain two spatial positions and the temporal order of cue presentation, new types of delay-period activity emerged; i.e., pair-dependent activity and temporal order-dependent activity. Both types of activity could be a mechanism for simultaneously retaining two items of spatial information and for effectively combining multiple spatial information by a single neuron. In addition, the presence of delay-period activity with position-dependency, pair-dependency and temporal order-dependency suggests that the dorsolateral prefrontal cortex plays an important role in planning sequential behaviors.

Animals↗
PubMed1998

Intraseptal injections of 192 IgG saporin produce deficits for strategy selection in spatial-memory tasks.

The involvement of the cholinergic septohippocampal system in strategies used to reach a spatial goal was examined by functionally inactivating this system with infusions of 192 IgG saporin, a potent cholinergic immunotoxin. Rats were initially trained on a win-shift radial arm maze (RAM) task and then given injections of either 192 IgG saporin (LES) or saline vehicle (CON) into the medial septum and vertical limb of the diagonal band. Rats were then retested postoperatively on the RAM to assess whether allocentric spatial strategies used to solve the task were impaired. The results indicated that injections of 192 IgG saporin into the septum of rats produced deficits in allocentric strategies used to locate the spatial goal when retested. In addition, place and response learning was also examined in a modified version of the Morris water maze task. In this task, rats with cholinergic lesions were mildly impaired in their ability to learn a place response. In order to clarify further whether rats may have been relying on allocentric or egocentric learning strategies to locate the platform, a probe trial was given on the final test day in which the visible platform was moved to a new location. Control rats swam either to the new platform location or the old platform location indicating the use of both an allocentric and egocentric response. However, rats with the cholinergic septal lesions swam to the new platform location indicating an egocentric response. Taken together, these results suggest that selective cholinergic lesions of the septum produce deficits in spatial strategies used to locate a spatial goal.

Animals↗
PubMed1997

The effect of nonspatial water maze pretraining in rats subjected to serotonin depletion and muscarinic receptor antagonism: a detailed behavioural assessment of spatial performance.

A detailed behavioural analysis of water maze spatial performance in the rat was utilized to determine the effect of single and combined administration of p-chlorophenylalanine (PCPA; 1000 mg/kg, i.p.), an inhibitor of serotonin biosynthesis, and scopolamine hydrobromide (SCO; 1.0 mg/kg, i.p.), a muscarinic receptor antagonist. In some groups a water maze pretraining regimen known as non-spatial pretraining (NSP) was used to familiarize the animals with the general requirements of the task before spatial training was begun. The results showed that: (a) depletion of serotonin with PCPA had no effect on water maze performance and produced no sensorimotor disturbances; (b) antagonism of muscarinic receptors produced impairments in spatial and sensorimotor function in naive rats but neither effect was observed in rats first given NSP; (c) combined disruption of muscarinic and serotonergic function produced a severe deficit in spatial performance that was only partially alleviated by NSP; and (d) there was an association between poor maze acquisition scores and a high incidence of sensorimotor dysfunction. In addition to the water maze task the rats were also assessed for motoric performance on a beam walking test. The role of cholinergic and serotonergic systems in learning and memory is discussed.

Animals↗
PubMed1997

Effect of active fragments of arginine-vasopressin on the disturbance of spatial cognition in rats.

The effect of arginine8-vasopressin (AVP1-9) and its metabolite C-terminal fragments on the scopolamine-induced disruption of spatial cognition were investigated using an 8-arm radial maze task in rats. AVP1-9 (10 micrograms/kg s.c.) markedly improved the disruption of spatial cognition by treatment with scopolamine (0.5 mg/kg i.p.), and 60% of the rats recovered to a normal level. The main metabolite of AVP1-9, AVP4-9 (0.5 and 1 ng/kg s.c.) also significantly improved the scopolamine-induced deficit of spatial memory. The activity of AVP4-9 was determined to be about 10000 fold greater than that of AVP1-9. An intracerebroventricular (i.c.v.) injection of 10 fg of AVP5-8, however, showed a lower activity. Both AVP6-8 and AVP5-7, which are both metabolites of AVP5-8, demonstrated no activity. The scopolamine-induced disruption of spatial memory was found to improve after a microinjection of AVP4-9 (1 fg) into the ventral hippocampus (VH) region, but not into the dorsal hippocampus (DH). In an in vivo microdialysis study, the scopolamine-induced acetylcholine (ACh) release from the VH was slightly potentiated by treatment with AVP4-9 (10 fg i.c.v.). In addition, an AVP4-9 analogue, No. 302, which is a synthetic hexapeptide and has a longer half-life, also demonstrated a markedly improved effect, which had a 10-fold higher activity than that with AVP4-9. AVP4-9 is the most potent activity of all the endogenous metabolites of the AVP1-9 and the new synthetic AVP4-9 analogue, No. 302 (obtained from Nippon Chemiphar Co.), substituting Ser for Cys-Cys in hexapeptide, has higher activity than that of AVP4-9. These results indicated [Ser6] hexapeptide has an important role in behavioral activity. Based on these results, it is possible that AVP1-9 and its metabolite AVP4-9 could, thus, be useful in treating cholinergic dysfunction diseases, such as Alzheimer's disease. Hexapeptide may play an important role in improving the spatial memory by promoting the release of ACh in the VH region.

Acetylcholine↗
PubMed1999

The effects of lesions to the caudolateral neostriatum on sun compass based spatial learning in homing pigeons.

To better define the role of the avian caudolateral neostriatum (NCL) in spatial behavior, we used homing pigeons to explore the effects of NCL lesions on a sun compass based spatial learning task. Although NCL lesioned birds learned the task, they required more sessions to reach criterion than controls. NCL lesioned pigeons were also able to acquire a color discrimination task that was procedurally similar to the sun compass spatial learning task, but they made more errors than controls. Both the deficits observed in sun compass based spatial learning and color discrimination were correlated with the volume of lesion damage to dorsal rather than ventral portions of NCL. Overall, these findings suggest that the role of NCL in homing pigeon navigation from distant unfamiliar locations is not related to a bird's ability to learn stimulus-direction associations using a sun compass. However NCL does appear involved in a pigeon's ability to perform at least some behaviors common to both the color discrimination and the sun compass based spatial learning tasks.

Animals↗