A role for anterior thalamic nuclei in affective cognition: Interaction with environmental conditions

Damage to anterior thalamic nuclei (ATN) is a well‐known cause of diencephalic pathology that produces a range of cognitive deficits reminiscent of a hippocampal syndrome. Anatomical connections of the ATN also extend to cerebral areas that support affective cognition. Enriched environments promote recovery of declarative/relational memory after ATN lesions and are known to downregulate emotional behaviors. Hence, the performance of standard‐housed and enriched ATN rats in a range of behavioral tasks engaging affective cognition was compared. ATN rats exhibited reduced anxiety responses in the elevated plus maze, increased activity and reduced corticosterone responses when exploring an open field, and delayed acquisition of a conditioned contextual fear response. ATN rats also exhibited reduced c‐Fos and phosphorylated cAMP response element‐binding protein (pCREB) immunoreactivity in the hippocampal formation and the amygdala after completion of the contextual fear test. Marked c‐Fos hypoactivity and reduced pCREB levels were also evident in the granular retrosplenial cortex and, to a lesser extent, in the anterior cingulate cortex. Unlike standard‐housed ATN rats, enriched ATN rats expressed virtually no fear of the conditioned context. These results show that the ATN regulate affective cognition and that damage to this region may produce markedly different behavioral effects as a function of environmental housing conditions. © 2013 Wiley Periodicals, Inc.     

Anterior thalamic nuclei lesions and recovery of function: Relevance to cognitive thalamus

Injury to the anterior thalamic nuclei (ATN) and their neural connections is the most consistent neuropathology associated with diencephalic amnesia. ATN lesions in rats produce memory impairments that support a key role for this region within an extended hippocampal system of complex overlapping neural connections. Environmental enrichment is a therapeutic tool that produces substantial, although incomplete, recovery of memory function after ATN lesions, even after the lesion-induced deficit has become established. Similarly, the neurotrophic agent cerebrolysin, also counters the negative effects of ATN lesions. ATN lesions substantially reduce c-Fos expression and spine density in the retrosplenial cortex, and reduce spine density on CA1 neurons; only the latter is reversed by enrichment. We discuss the implications of this evidence for the cognitive thalamus, with a proposal that there are genuine interactions among different but allied thalamo-cortical systems that go beyond a simple summation of their separate effects.     

Retrosplenial cortex lesions of area Rgb (but not of area Rga) impair spatial learning and memory in the rat

The retrosplenial cortex, which is situated in a critical position in the flow of information between the hippocampal formation and the neocortex, contributes to spatial memory, but no studies have examined the distinct contribution of each area of the retrosplenial cortex to this behavior. This study tests the hypothesis that the two areas of the retrosplenial granular cortex play distinct roles in spatial learning and memory. Adult, male Sprague-Dawley rats with small, bilateral lesions (ibotenic acid) of the retrosplenial granular cortex were tested for 2 weeks in a repeated acquisition water maze task. Compared to controls, rats with complete lesions of the retrosplenial granular b cortex (Rgb) were slightly, but significantly impaired, whereas rats with lesions of the retrosplenial granular a cortex (Rga) displayed no impairment. Further, the Rgb-lesioned (but not the Rga-lesioned) group was impaired in the probe trials at the end of the first week of training. All animals were tested in the same paradigm for a second week to determine if the learning and memory impairment in the Rgb-lesioned rats simply reflected "delayed learning." All animals improved their maze performance during the second week of testing, but the Rgb-lesioned group still had no preference for the correct quadrant in the probe trial. Together, these data indicate that Rgb plays a small, independent role in spatial learning and memory. Further, although selective lesions of Rga or Rgb do not cause a large deficit in learning, concomitant destruction of both areas causes a much greater impairment in learning than would be predicted from their independent contributions. The data highlight the unique and complex contribution of each area of the retrosplenial cortex to behavior.     

环境富集对孕期应激子代青年期大鼠海马突触损害的影响

Environmental enrichment attenuates hippocampal synaptic injury induced by prenatal stress in offspring. However, the influence of hippocampal synaptic changes and regional differences in prenatal stress remains poorly understood. The present study induced stress in Sprague Dawley rats, which were at gestational age 13-19 days. Following weaning, the offspring were raised in an enriched environment to establish models of stress + enriched environment. Dendritic spine density and synaptophysin expression were detected in hippocampal neurons using Golgi staining and western blot analysis, respectively. Results showed that enriched environment increased dendritic spine density of apical dendrites in CA1 pyramidal cells and basal dendrites of granular cells in the outer layer of the dentate gyrus. In addition, hippocampal synaptophysin expression increased and the effects of prenatal stress on neuronal dendritic spines were reversed in adolescence.     

Olfactory learning-induced increase in spine density along the apical dendrites of CA1 hippocampal neurons

We have previously shown that rule learning of an olfactory discrimination task is accompanied by increased spine density along the apical dendrites of piriform cortex pyramidal neurons. The purpose of the present study was to examine whether such olfactory learning task, in which the hippocampus is actively involved, induces morphological modifications in CA1 pyramidal neurons as well. Rats were trained to discriminate positive cues in pairs of odors for a water reward. Morphological modifications were studied in Golgi-impregnated neurons with light microscopy, 1 and 3 days after training completion. Spine densities were measured on the proximal region of apical dendrites and on basal dendrites after rule learning. Three days after training completion, the mean spine density on apical dendrites in neurons from trained rats was significantly higher by 20.5% than in neurons from pseudo-trained and naive animals, which did not differ from each other. By contrast, there was no significant difference in spine density of basal dendrites among the three groups. As length and diameter of spiny dendritic segments did not change after learning, the learning-related increase in spine density in neurons from trained rats may reflect a net increase in the number of excitatory synapses in the hippocampus following olfactory rule learning.     

Chronic 17β‐estradiol or cholesterol prevents stress‐induced hippocampal CA3 dendritic retraction in ovariectomized female rats: Possible correspondence between CA1 spine properties and spatial acquisition

Chronic stress may have different effects on hippocampal CA3 and CA1 neuronal morphology and function depending upon hormonal status, but rarely are manipulations of stress and gonadal steroids combined. Experiment 1 investigated the effects of chronic restraint and 17β‐estradiol replacement on CA3 and CA1 dendritic morphology and spatial learning in ovariectomized (OVX) female Sprague–Dawley rats. OVX rats were implanted with 25% 17β‐estradiol, 100% cholesterol, or blank silastic capsules and then chronically restrained (6h/d/21d) or kept in home cages. 17β‐Estradiol or cholesterol prevented stress‐induced CA3 dendritic retraction, increased CA1 apical spine density, and altered CA1 spine shape. The combination of chronic stress and 17β‐estradiol facilitated water maze acquisition compared to chronic stress + blank implants and nonstressed controls + 17β‐estradiol. To further investigate the interaction between 17β‐estradiol and stress on hippocampal morphology, experiment 2 was conducted on gonadally intact, cycling female rats that were chronically restrained (6h/d/21d), and then euthanized at proestrus (high ovarian hormones) or estrus (low ovarian hormones). Cycling female rats failed to show chronic stress‐induced CA3 dendritic retraction at either estrous phase. Chronic stress enhanced the ratio of CA1 basal spine heads to headless spines as found in experiment 1. In addition, proestrous rats displayed increased CA1 spine density regardless of stress history. These results show that 17β‐estradiol or cholesterol protect against chronic stress‐induced CA3 dendritic retraction in females. These stress‐ and 17β‐estradiol‐induced morphological changes may provide insight into how dendritic complexity and spine properties contribute to spatial ability. © 2009 Wiley‐Liss, Inc.     

Diversity and fluctuation of spine morphology in CA1 pyramidal neurons after transient global ischemia

Dendritic spines form postsynaptic components of excitatory synapses in CA1 pyramidal neurons and play a key role in excitatory signal transmission. Transient global ischemia is thought to induce excitotoxicity that triggers delayed neuronal death in the CA1 region. However, the mechanism underlying structural changes of excitatory synapses after ischemia is not completely understood. Here, we demonstrate how dendritic spines change in their density and structure at an acute stage after transient global ischemia. Intracellular staining in vivo showed that the total spine density in basal, proximal, and distal apical dendrites increased at 12 hr and 24 hr after ischemia, but returned to control levels at 48 hr after ischemia. Consistent increase of spine density mainly appeared in non-late depolarizing postsynaptic potential neurons, although late depolarizing postsynaptic potential neurons also showed slight increases in spine density in these dendrites at the same intervals after ischemia. Golgi staining showed increased spine density occurred in less swollen dendrites but decreased spine density appeared in severely swollen dendrites at 12 and 24 hr after ischemia. In addition, the density and percentage of stubby spines reduced at 12 hr and 48 hr, whereas the density of thin spines increased at 12 hr after ischemia. The density and percentage of filopodia increased nearly fivefold at 24 hr after ischemia. Moreover, the density of mushroom spines doubled and its percentage increased by 150% at 48 hr after ischemia. These morphological changes of spines may be related to neuronal injury in CA1 pyramidal neurons after ischemia.     

Dynamic changes in CA1 dendritic spines associated with ischemic tolerance

Hippocampal CA1 neurons are particularly vulnerable to 5-10 min durations of global ischemia. These cells can develop tolerance to ischemia through prior exposure to brief episodes of ischemia (ischemic preconditioning, IP). Dendritic spines are implicated in various forms of neuroplasticity including memory and recovery of function. Here we characterized the changes in hippocampal CA1 dendritic spines during the development of ischemic tolerance and the subsequent postischemic recovery period. Gerbils received 5 min, bilateral carotid artery occlusions preceded by two 1.5 min occlusions each of which were 24 h apart (tolerance groups). Spine densities were calculated from CA1 apical and basilar dendrites in tolerant animals that survived 3 (IP3), 10 (IP10) or 30 (IP30) days as well as sham-operated animals and those that received only the two preconditioning episodes (PO). Habituation to a novel open-field was assessed 3, 7, 10 and 30 days after ischemia to gauge CA1 functional integrity. Dendritic spines were quantified from Golgi-Cox stained sections of the CA1 subfield. IP10, IP30 and PO animals had significantly higher CA1 basilar and apical spine densities than all other groups. Tolerant animals initially displayed open-field habituation impairments at a time when spine densities were reduced. Behavioral impairments gradually subsided over time in coincidence with an increase in CA1 spine densities. These findings suggest that dendritic spines may play a role in recovery of function associated with ischemic tolerance and stroke.     

Corticosterone reduces dendritic complexity in developing hippocampal CA1 neurons

Although prolonged stress and corticosteroid exposure induce morphological changes in the hippocampal CA3 area, the adult CA1 area is quite resistant to such changes. Here we addressed the question whether elevated corticosteroid hormone levels change dendritic complexity in young, developing CA1 cells. In organotypic cultures (prepared from P5 rats) that were 14–21 days cultured in vitro, two doses of corticosterone (30 and 100 nM) were tested. Dendritic morphology of CA1 neurons was established by imaging neurons filled with the fluorescent dye Alexa. Application of 100 nM corticosterone for 20 minutes induced atrophy of the apical dendritic tree 1–4 hours later. Fractal analysis showed that total neuronal complexity was reduced twofold when compared with vehicle‐treated neurons. Exposing organotypic slices to 30 nM corticosterone reduced apical length in a more delayed manner: only neurons examined more than 2 hours after exposure to corticosterone showed atrophy of the apical dendritic tree. Neither dose of corticosterone affected the length of basal dendrites or spine density. Corticosterone was ineffective in changing morphology of the apical dendrites when tested in the presence of the glucocorticoid receptor antagonist RU38486. These results suggest that high physiological levels of corticosterone, via activation of the glucocorticoid receptor, can, during the course of only a few hours, reduce the dendritic complexity of CA1 pyramidal neurons in young, developing hippocampal tissue. These findings suggest that it is relevant to maintain plasma corticosterone levels low during hippocampal development. © 2009 Wiley‐Liss, Inc.     

Age-related alterations in hippocampal spines and deficiencies in spatial memory in mice

Alterations in neuronal morphology occur in the brain during normal aging, but vary depending on neuronal cell types and brain regions. Such alterations have been related to memory and cognitive impairment. Changes in hippocampal spine densities are thought to represent a morphological correlate of altered brain functions associated with hippocampal-dependent learning and memory. We therefore have analyzed the impact of aging on different hippocampal-dependent learning tasks and on changes in dendritic spines of CA1 hippocampal and dentate gyrus neurons by analyzing adult (6-7 months) and aged (21-22 months) C57/Bl6 mice. We found a significant decrease in spine numbers of basal CA1 dendrites and decreases in spine length of apical dendrites of CA1 and dentate gyrus neurons. Furthermore, aged mice exhibited significant deficits in hippocampus-dependent learning tasks, such as the probe trial of the Morris water maze and T maze learning. Given the fact that there is no neuronal loss in the hippocampus in aged mice (von Bohlen und Halbach and Unsicker [2002] Eur. J. Neurosci. 16:2434-2440), we suggest that the memory and cognitive decline in the context of aging may be accompanied by rather subtle anatomical changes, such as numbers and morphology of dendritic spines.     

Influence of predator stress on the consolidation versus retrieval of long-term spatial memory and hippocampal spinogenesis

We have studied the influence of predator stress (30 min of cat exposure) on long-term (24 h) spatial memory and the density of spines in basilar dendrites of CA1 neurons. Predator stress occurred either immediately before water maze training (Stress Pre-Training) or before the 24 h memory test (Stress Pre-Retrieval). The Control (nonstress) group exhibited excellent long-term spatial memory and a robust increase in the density of stubby, but not mushroom, shaped spines. The Stress Pre-Training group had impaired long-term memory and did not exhibit any changes in spine density. The Stress Pre-Retrieval group was also impaired in long-term memory performance, but this group exhibited an increase in the density of stubby, but not mushroom, shaped spines, which was indistinguishable from the control group. These findings indicate that: (1) A single day of water maze training under control conditions produced intact long-term memory and an increase in the density of stubby spines in CA1; (2) Stress before training interfered with the consolidation of information into long-term memory and suppressed the training-induced increase in spine density; and (3) Stress immediately before the 24 h memory test trial impaired the retrieval of the stored memory, but did not reverse the training-induced increase in CA1 spine density. Overall, this work provides evidence of structural plasticity in dendrites of CA1 neurons which may be involved in the consolidation process, and how spinogenesis and memory are modulated by stress.     

Regulation of hippocampal dendritic spines following sleep deprivation

Accumulating evidence supports the role of sleep in synaptic plasticity and memory consolidation. One line of investigation, the synaptic homeostasis hypothesis, has emphasized the increase in synaptic strength during waking, and compensatory downsizing of (presumably less frequently used) synapses during sleep. Conversely, other studies have reported downsizing and loss of dendritic spines following sleep deprivation. We wanted to determine the effect of sleep deprivation on dendritic spines of hippocampal CA1 neurons using genetic methods for fluorescent labeling of dendritic spines. Male Vglut2-Cre mice were injected with an AAV-DIO-ChR2-mCherry reporter in CA1 hippocampus. Gentle handling was used to sleep deprive mice for 5 hr, from lights on (7 am ) to 12 noon. Control and sleep-deprived mice were euthanized at 12 noon and processed for quantification of dendritic spines. We used confocal microscope imaging and three-dimensional (3D) analysis to quantify thin, mushroom, and stubby spines from CA1 dendrites, distinguishing between branch segments. We observed significantly greater density of spines in CA1 of sleep-deprived mice, driven primarily by greater numbers of thin spines, and significantly larger spine volume and head diameter. Branch and region-specific analysis revealed that spine volume was greater in primary dendrites of apical and basal segments, along with proximal segments on both apical and basal dendrites, and spine density was increased in secondary branches and distal segments on apical dendrites following sleep deprivation. Our 3D quantification suggests sleep contributes to region- and branch-specific synaptic downscaling in the hippocampus, supporting the theory of broad but selective synaptic downscaling during sleep.     

Behavioral training interferes with the ability of gonadal hormones to increase CA1 spine synapse density in ovariectomized female rats

Estradiol benzoate (EB) has repeatedly been shown to increase hippocampal CA1 spine synapse density in ovariectomized female rats. Although this increase has been assumed to enhance memory, a direct link between increased spine synapse density and memory has not been demonstrated. Furthermore, while androgens, such as testosterone propionate (TP) and dihydrotestosterone (DHT), also increase spine synapse density in females, their effects on memory have yet to be investigated. In the present study, ovariectomized female rats were given two injections, 24 h apart, of sesame oil (control), 10 µg EB, 500 µg TP or 500 µg DHT. Forty‐eight hours after the second injection, rats were tested in a 1‐day spatial Morris water maze task and then immediately perfused for analysis of CA1 spine synapse density (using electron microscopy and unbiased stereology). In the spatial acquisition phase of testing, EB, but not TP or DHT, significantly impaired memory relative to controls. Hormone treatment did not affect spatial retention or performance in the non‐spatial phase of testing. In contrast to previous work, spine synapse density was not increased by EB, TP or DHT. We therefore examined a new set of EB‐treated females, only half of which were water maze tested. Consistent with previous work, EB significantly increased spine synapse density among behaviorally naïve females. In contrast, spine synapse densities did not differ among behaviorally tested control and EB females, although they were higher than behaviorally naïve controls. These data indicate that 1‐day water maze testing can eliminate the hormone‐induced increases in CA1 spine synapse density typically observed in behaviorally naïve females.     

Tau phosphorylation‐associated spine regression does not impair hippocampal‐dependent memory in hibernating golden hamsters

The microtubule‐associated protein tau, in its hyperphosphorylated form, is the major component of paired helical filaments and other aggregates in neurodegenerative disorders commonly referred to as “tauopathies”. Recent evidence, however, indicates that mislocalization of hyperphosphorylated tau to subsynaptic sites leads to synaptic impairment and cognitive decline even long before formation of tau aggregates and neurodegeneration occur. A similar, but reversible hyperphosphorylation of tau occurs under physiologically controlled conditions during hibernation. Here, we study the hibernating Golden hamster (Syrian hamster, Mesocricetus auratus). A transient spine reduction was observed in the hippocampus, especially on apical dendrites of hippocampal CA3 pyramidal cells, but not on their basal dendrites. This distribution of structural synaptic regression was correlated to the distribution of phosphorylated tau, which was highly abundant in apical dendrites but hardly detectable in basal dendrites. Surprisingly, hippocampal memory assessed by a labyrinth maze was not affected by hibernation. The present study suggests a role for soluble hyperphosphorylated tau in the process of reversible synaptic regression, which does not lead to memory impairment during hibernation. We hypothesize that tau phosphorylation associated spine regression might mainly affect unstable/dynamic spines while sparing established/stable spines. © 2015 Wiley Periodicals, Inc.     

Dendritic morphology of neurons in medial prefrontal cortex and hippocampus in 2VO rats

Cerebral ischemia is the main cause of cognitive impairment. Changes in dendritic morphology and spines have been shown to occur with synaptic plasticity and cognitive function. Bilateral occlusion of the common carotid arteries (2VO) in rats was an effective model of chronic cerebral ischemia. In this experiment, SD rats were divided into model group (2VO) and sham-operated group. At 2, 4, 8 and 16?weeks, rats were tested in Morris water maze to observe learning and memory abilities, and then the brain tissue was stained by Golgi method to investigate the morphology of dendrites of pyramidal neurons under light microscope. Dendritic length and arborization and spine density of pyramidal neurons in medial prefrontal cortex (mPFC) and hippocampal CA1 were analyzed by ImageJ. Progressive learning and memory deficits appeared since 2?weeks. Compared to the sham-operated group, the dendritic length and arborization significantly decreased in the model group at 4, 8 and 16?weeks after 2VO in CA1, while there was no significant difference in mPFC. Dendritic spine density in hippocampal CA1 of the model group significantly decreased after 2?weeks, and it was decreased after 8?weeks in mPFC. The results suggest that under the condition of chronic cerebral ischemia, the alteration of dendritic morphology and spine density underlay cognitive impairment.     

Dendritic spine density of adult hippocampal pyramidal cells is sensitive to thyroid hormone

In order to determine whether pyramidal cells of the adult hippocampus are morphologically sensitive to thyroid hormone, we performed single-section Golgi impregnation analyses on brains from hyperthyroid and control rats. Quantitative analyses of Golgi-impregnated pyramidal cells from the CA1 region showed a significant decrease in the density of apical dendritic spines with hyperthyroidism. In contrast, no changes were observed in spine density of basal dendrites or in cross-sectional cell body area of CA1 pyramidal cells. No changes in any of these morphological variables were detected in pyramidal cells of the CA3 region with hyperthyroidism. These results suggest that spine density of the apical dendrites of CA1 pyramidal cells is specifically affected by thyroid hormone in adulthood. Since dendritic spines are thought to represent postsynaptic sites it is likely that this morphological change results in altered hippocampal function.     

Cytosine arabinoside treatment impairs the remote spatial memory function and induces dendritic retraction in the anterior cingulate cortex of rats

Clinical studies on cancer patients have revealed that chemotherapy is associated with long-term cognitive impairment. In the present study, we used a rat model to evaluate the effects of the anticancer drug cytosine arabinoside (Ara-C) on spatial learning, memory, and the dendritic morphology of neurons in the anterior cingulate cortex (ACC) and hippocampus. The drug was observed to induce deficits in the long-term spatial memory function but not in the spatial learning and recent memory, as was assessed by performing the Morris water maze test. In the Ara-C treated rats, retraction of the apical dendrites was noted in the neurons in the ACC but not in the pyramidal neurons in the hippocampal region CA1. Our in vivo adult rat model of neurotoxicity provides data on the long-term cognitive and cellular morphometric alterations in the frontal lobes induced by Ara-C treatment. Retraction of the apical dendrites of the pyramidal neurons in the ACC may contribute to the remote spatial memory impairment induced by Ara-C treatment.     

Connections between the retrosplenial cortex and the hippocampal formation in the rat: a review.

The retrosplenial cortex is situated at the crossroads between the hippocampal formation and many areas of the neocortex, but few studies have examined the connections between the hippocampal formation and the retrosplenial cortex in detail. Each subdivision of the retrosplenial cortex projects to a discrete terminal field in the hippocampal formation. The retrosplenial dysgranular cortex (Rdg) projects to the postsubiculum, caudal parts of parasubiculum, caudal and lateral parts of the entorhinal cortex, and the perirhinal cortex. The retrosplenial granular b cortex (Rgb) projects only to the postsubiculum, but the retrosplenial granular a cortex (Rga) projects to the postsubiculu, rostral presubiculum, parasubiculum, and caudal medial entorhinal cortex. Reciprocating projections from the hippocampal formation to Rdg originate in septal parts of CA1, postsubiculum, and caudal parts of the entorhinal cortex, but these are only sparse projections. In contrast, Rgb and Rga receive dense projections from the hippocampal formation. The hippocampal projection to Rgb originates in area CA1, dorsal (septal) subiculum, and post-subiculum. Conversely, Rga is innervated by ventral (temporal) subiculum and postsubiculum. Further, the connections between the retrosplenial cortex and the hippocampal formation are topographically organized. Rostral retrosplenial cortex is connected primarily to the septal (rostrodorsal) hippocampal formation, while caudal parts of the retrosplenial cortex are connected with temporal (caudoventral) areas of the hippocampal formation. Together, the elaborate connections between the retrosplenial cortex and the hippocampal formation suggest that this projection provides an important pathway by which the hippocampus affects learning, memory, and emotional behavior.     

A mental retardation gene,motopsin /neurotrypsin /prss12, modulates hippocampal function and social interaction

Motopsin is a mosaic serine protease secreted from neuronal cells in various brain regions, including the hippocampus. The loss of motopsin function causes nonsyndromic mental retardation in humans and impairs long‐term memory formation in Drosophila. To understand motopsin’s function in the mammalian brain, motopsin knockout (KO) mice were generated. Motopsin KO mice did not have significant deficits in memory formation, as tested using the Morris water maze, passive avoidance and Y‐maze tests. A social recognition test showed that the motopsin KO mice had the ability to recognize two stimulator mice, suggesting normal social memory. In a social novelty test, motopsin KO mice spent a longer time investigating a familiar mouse than wild‐type (WT) mice did. In a resident–intruder test, motopsin KO mice showed prolonged social interaction as compared with WT mice. Consistent with the behavioral deficit, spine density was significantly decreased on apical dendrites, but not on basal dendrites, of hippocampal pyramidal neurons of motopsin KO mice. In contrast, pyramidal neurons at the cingulate cortex showed normal spine density. Spatial learning and social interaction induced the phosphorylation of cAMP‐responsive element‐binding protein (CREB) in hippocampal neurons of WT mice, whereas the phosphorylation of CREB was markedly decreased in mutant mouse brains. Our results indicate that an extracellular protease, motopsin, preferentially affects social behaviors, and modulates the functions of hippocampal neurons.     

Prefrontocortical serotonin depletion results in plastic changes of prefrontocortical pyramidal neurons, underlying a greater efficiency of short-term memory

The prefrontal cortex activity is involved in organizing the short-term memory. Although the involvement of serotonin for an appropriate performance in learning and memory tests is well known, its role is still unclear; as is the cellular basis of short-term memory behavioral performance. Sprague-Dawley rats were stereotactically injected with 1 microg/microl of 5, 7-dihydroxitryptamine to cause a lesion to the dorsal raphe nucleus. Sham-operated or intact rats were also studied as control groups. Before surgery and 20 days post-operatively, each animal was placed in the Biel maze for five consecutive trials. In the pre-treatment test, all three groups decreased significantly the number of errors beginning with the fourth trial. The same occurred in the post-treatment test, except for the experimental group, whose animals committed less errors beginning with the second trial. After behavioral testing, the dorsomedial prefrontal cerebral cortex was dissected out, and the Golgi study of the third-layer pyramidal neurons revealed that the length of both the apical and the basilar dendrites was smaller than that of controls, and that the apical and oblique dendrites had a greater spine density. A major proportion of thin spines was also seen on the basilar and oblique dendrites, and more stubby spines were seen on the apical dendrite. Serotonin depletion in the prefrontal cerebral cortex resulted in cytoarchitectural alterations of the prefrontocortical pyramidal neurons, which may be underlying partially the greater efficiency observed in the short-term memory behavioral performance.