Region-specific alteration of GABAergic markers in the brain of heterozygous reeler mice.

Heterozygous reeler mice (HRM), haploinsufficient for reelin, have been proposed to be a genetic mouse model of schizophrenia. Beside behavioural similarities, HRM also demonstrate several neuroanatomical traits similar to patients suffering from schizophrenia. In the present study using immunocytochemical procedures, we investigated HRM and wild-type mice (WT) for differences in the numbers and densities of glutamic acid decarboxylase (GAD)67 and parvalbumin (PARV)-immunoreactive (IR) neurons in the hippocampus, tyrosine hydroxylase (TH)-IR neurons in the ventral tegmental area (VTA) and substantia nigra (SN), and serotonin transporter (5-HT-T)-IR neurons of the raphe nuclei. We found that HRM, compared with WT, show a significant decrease of GAD67-IR neurons in hippocampal subregion CA1 [stratum pyramidale (SP)], CA2 [stratum oriens (SO), stratum pyramidale (SP) and stratum radiatum (SR)] and dentate gyrus [granule cell layer (GL)], and also a significant decrease of PARV-containing neurons in CA1 (SO, SP) and CA2 (SP). No morphological differences were found in the SN/VTA or raphe nuclei. In conclusion, these results support a hippocampal γ-aminobutyric acid (GABA)ergic dysfunction in HRM as previously described by other authors, and may be based on a downregulation of GAD67 and PARV expressions. In summary, the reelin haploinsufficient mouse may provide a useful model for studying the interaction between reelin and hippocampal GABAergic system, its effect on dendritic spine maturation and plasticity related to schizophrenia.

Reduction of Prepulse Inhibition (PPI) after neonatal excitotoxic lesion of the ventral thalamus in pubertal and adult rats.

BACKGROUND: Growing evidence indicates the role of the thalamus in schizophrenia. The ventral part of the thalamus has been investigated in a few post-mortem studies, suggesting a possible neurodevelopmental etiology of the reduced neuron number. METHODS: Here we adapt a neurodevelopmental animal model, the neonatal excitotoxic brain lesion, to the ventral thalamus (VT) of Sprague-Dawley rats. At postnatal day (PD) 7 male pups were bilaterally infused into the VT using ibotenic acid (IBA) or artificial cerebrospinal fluid. Repeated measurements of prepulse inhibition (PPI) of the acoustic startle response, reviewed as a measure of sensorimotor gating deficits in neuropsychiatric disorders such as schizophrenia, were performed during puberty and adulthood. RESULTS: IBA animals showed lower PPI (p<0.001) compared to controls. The extent of VT lesions correlated negatively with PPI levels (p<0.001). PPI deficits in IBA animals were observed at PD 43 and PPI levels increased significantly after puberty without reaching control levels. Acute or subchronic clozapine treatment did not significantly restore low PPI in IBA rats. CONCLUSION: The present data suggest that the VT may be involved in the PPI deficits observed in schizophrenia.

Centromere and telomere movements during early meiotic prophase of mouse and man are associated with the onset of chromosome pairing.

The preconditions and early steps of meiotic chromosome pairing were studied by fluorescence in situ hybridization (FISH) with chromosome-specific DNA probes to mouse and human testis tissue sections. Premeiotic pairing of homologous chromosomes was not detected in spermatogonia of the two species. FISH with centromere- and telomere-specific DNA probes in combination with immunostaining (IS) of synaptonemal complex (SC) proteins to testis sections of prepuberal mice at days 4-12 post partum was performed to study sequentially the meiotic pairing process. Movements of centromeres and then telomeres to the nuclear envelope, and of telomeres along the nuclear envelope leading to the formation of a chromosomal bouquet were detected during mouse prophase. At the bouquet stage, pairing of a mouse chromosome-8-specific probe was observed. SC-IS and simultaneous telomere FISH revealed that axial element proteins appear as large aggregates in mouse meiocytes when telomeres are attached to the nuclear envelope. Axial element formation initiates during tight telomere clustering and transverse filament-IS indicated the initiation of synapsis during this stage. Comparison of telomere and centromere distribution patterns of mouse and human meiocytes revealed movements of centromeres and then telomeres to the nuclear envelope and subsequent bouquet formation as conserved motifs of the pairing process. Chromosome painting in human spermatogonia revealed compacted, largely mutually exclusive chromosome territories. The territories developed into long, thin threads at the onset of meiotic prophase. Based on these results a unified model of the pairing process is proposed.

Postnatal modification of hippocampal circuitry alters avoidance learning in adult rats.

In rats and mice, the genetically mediated extent of the mossy fiber projection that synapses on the basal dendrites of hippocampal pyramidal cells is inversely correlated with rate of two-way avoidance (shuttle-box) learning. Postnatal hyperthyroidism, induced in 51 rat pups, resulted in marked variations of this infrapyramidal mossy fiber projection. The number of trials required for criterion performance of these rats in adulthood remained correlated with the neuroanatomical trait (r = 0.74, P less than 0.0001).

Individual hippocampal mossy fiber distribution in mice correlates with two-way avoidance performance.

Mice systematically bred for randomization of their genotype show large individual differences when performing a two-way avoidance task (shuttle-box learning). Their behavioral scores correlate strongly (r = -0.80, P less than .01) with the number of mossy fibers synapsing on basal dendrites of hippocampal pyramidal neurons, poor avoiders having relatively more such terminals. This confirms previous findings showing that rat and mouse strains known for genetically dependent poor avoidance learning have extended intra- and infrapyramidal mossy fiber projections.

Systems biology and addiction.

The onset of addiction is marked with drug induced positive experiences that keep being repeated. During that time, adaptation occurs and addiction is stabilized. Interruption of those processes induces polysymptomatic withdrawal syndromes. Abstinence is accompanied by risks of relapse. These features of addiction suggest adaptive brain dynamics with common pathways in complex neuronal networks. Addiction research has used animal models, where some of those phenomena could be reproduced, to find correlates of addictive behavior. The major thrust of those approaches has been on the involvement of genes and proteins. Recently, an enormous amount of data has been obtained by high throughput technologies in these fields. Therefore, (Computational) "Systems Biology" had to be implemented as a new approach in molecular biology and biochemistry. Conceptually, Systems Biology can be understood as a field of theoretical biology that tries to identify patterns in complex data sets and that reconstructs the cell and cellular networks as complex dynamic, self-organizing systems. This approach is embedded in systems science as an interdisciplinary effort to understand complex dynamical systems and belongs to the field of theoretical neuroscience (Computational Neuroscience). Systems biology, in a similar way as computational neuroscience is based on applied mathematics, computer-based computation and experimental simulation. In terms of addiction research, building up "computational molecular systems biology of the (addicted) neuron" could provide a better molecular biological understanding of addiction on the cellular and network level. Some key issues are addressed in this article.

A quantitative-genetic analysis of hippocampal variation in the mouse.

This report analyses the genetic underpinnings of the proportions of the hippocampal terminal fields in the mouse at the midseptotemporal level. We used 5 inbred strains and all possible F(1) crosses between them (diallel cross). Broad heritabilities ranged from 11 to 53%. Additive genetic variation was present for all phenotypes analyzed. Directional dominance was found for the relative size of the suprapyramidal mossy fiber terminal field only. For the stratum lacunosum-moleculare, ambidirectional dominance emerged. These findings suggest that, in evolutionary history, directional selection has operated for a proportionally large suprapyramidal terminal field. For all other hippocampal variables (viz. the relative sizes for the strata oriens, pyramidale, radiatum, lacunosum-moleculare, CA4, intra- and infrapyramidal mossy fiber terminal field and the absolute size of the regio inferior) past stabilizing selection was inferred.

Disrupted visceral feedback reduces locomotor activity and influences background contextual fear conditioning in C57BL/6JOlaHsd mice.

The present experiments were designed to study fear conditioning as an emotional learning task with disrupted visceral feedback. For that purpose we used the peripherally acting beta1-adrenoceptor blocker atenolol and studied its effects on the behavior of male C57BL/6JOlaHsd mice in an exploration-related test and during fear-conditioning. In the first experiment, we treated mice with saline or different doses of the beta1-adrenergic blocker atenolol (5mg/kg and 20mg/kg body weight i.p.) 30 min before behavioral testing in a motility box. Only the high but not the low dose of atenolol led to a reduction of locomotor activity (p<0.02). Factors known to be related to emotionality (rearing, area preference) were unaffected. In a second experiment, saline- and atenolol-treated mice (same dosages and mode of application) were trained for auditory fear conditioning, and 24h later they were retested in the same environment. We found differences between the effects of atenolol upon contextual- and cue-fear conditioning. Animals treated with 20mg/kg BW doses of atenolol showed significantly decreased background contextual fear compared to saline-treated control animals. In contrast, no differences were found during CS presentation in the conditioning context between atenolol-treated animals and saline-treated controls, independent from a paired or an unpaired conditioning paradigm. Thus, the blockade of peripheral beta1-adrenoceptors by atenolol may have disrupted the positive feedback to the central nervous system via visceral afferents resulting in a decreased locomotor activity and background contextual fear.

Structure-function integrity of the adult hippocampus depends on the transcription factor Bcl11b/Ctip2.

The dentate gyrus is one of the only two brain regions where adult neurogenesis occurs. Throughout life, cells of the neuronal stem cell niche undergo proliferation, differentiation and integration into the hippocampal neural circuitry. Ongoing adult neurogenesis is a prerequisite for the maintenance of adult hippocampal functionality. Bcl11b, a zinc finger transcription factor, is expressed by postmitotic granule cells in the developing as well as adult dentate gyrus. We previously showed a critical role of Bcl11b for hippocampal development. Whether Bcl11b is also required for adult hippocampal functions has not been investigated. Using a tetracycline-dependent inducible mouse model under the control of the forebrain-specific CaMKIIα promoter, we show here that the adult expression of Bcl11b is essential for survival, differentiation and functional integration of adult-born granule cell neurons. In addition, Bcl11b is required for survival of pre-existing mature neurons. Consequently, loss of Bcl11b expression selectively in the adult hippocampus results in impaired spatial working memory. Together, our data uncover for the first time a specific role of Bcl11b in adult hippocampal neurogenesis and function.

Separate sets of neurons of the central nucleus of the amygdala project to the substantia innominata and the caudal pontine reticular nucleus in the rat.

The central nucleus of the amygdala (CeA) is generally regarded as a control nucleus of subcortical target systems. Due to its widespread projections to different brain areas it is able to modulate emotional behavior of the organism. However, it is still not clear whether single neurons of the CeA project to different areas or to one target area. Injections of the retrograde tracers Fluorogold and True Blue into target regions of the central nucleus of the amygdala, i.e., the substantia innominata (SI) and the caudal pontine reticular nucleus (PNC), revealed overlapping but otherwise distinct neuronal populations within mainly the medial division of the CeA. From our study we conclude that SI and PNC receive input from different subsets of amygdala neurons.

TMT predator odor activated neural circuit in C57BL/6J mice indicates TMT-stress as a suitable model for uncontrollable intense stress.

Intense stressful events can result in chronic disorders such as posttraumatic stress disorder (PTSD). In vulnerable individuals, a single aversive experience can be sufficient to cause long-lasting behavioral changes. Candidate brain regions implicated in stress-related psychopathology are the amygdala, the bed nucleus of the stria terminalis (BNST), and the hypothalamic pituitary adrenal (HPA) axis. In rodents exposure to 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), an ethologically relevant stressor, has been shown to induce intense stress and innate anxiety responses. To study dispositions for the development of maladaptive stress responses, mice models are required. Therefore C57BL/6J mice were exposed to TMT and Fos expression was studied in key brain regions implicated in stress responses and anxiety-like behavior. Our results show TMT-induced activation of a distinct neural circuit involving the BNST, the lateral septum (LS), the paraventricular nucleus of the hypothalamus (PVN), the periaqueductal gray (PAG) and the locus coeruleus (LC). Anatomical interconnection of the BNST with all these regions could point to an important modulatory role of this nucleus. Since, the BNST gets direct input from the olfactory bulbs and projects to the PVN and PAG and is therefore well positioned to modulate behavioral and endocrine stress responses to TMT. Hence, we suggest that TMT exposure is suitable to investigate uncontrollable stress responses in mice which exhibit similarities to maladaptive stress responses underlying PTSD in humans.

Direct synaptic connections of axons from superior colliculus with identified thalamo-amygdaloid projection neurons in the rat: possible substrates of a subcortical visual pathway to the amygdala.

The aim of the present study was to identify synaptic contacts from axons originating in the superior colliculus with thalamic neurons projecting to the lateral nucleus of the amygdala. Axons from the superior colliculus were traced with the anterograde tracers Phaseolus vulgaris leucoagglutinin or the biotinylated and fluorescent dextran amine "Miniruby." Thalamo-amygdaloid projection neurons were identified with the retrograde tracer Fluoro-Gold. Injections of Fluoro-Gold into the lateral nucleus of the amygdala labeled neurons in nuclei of the posterior thalamus which surround the medial geniculate body, viz. the suprageniculate nucleus, the medial division of the medial geniculate body, the posterior intralaminar nucleus, and the peripeduncular nucleus. Anterogradely labeled axons from the superior colliculus terminated in the same regions of the thalamus. Tecto-thalamic axons originating from superficial collicular layers were found predominantly in the suprageniculate nucleus, whereas axons from deep collicular layers were detected in equal density in all thalamic nuclei surrounding the medial geniculate body. Double-labeling experiments revealed an overlap of projection areas in the above-mentioned thalamic nuclei. Electron microscopy of areas of overlap confirmed synaptic contacts of anterogradely labeled presynaptic profiles originating in the superficial layers of the superior colliculus with retrogradely labeled postsynaptic profiles of thalamo-amygdaloid projection neurons. These connections may represent a subcortical pathway for visual information transfer to the amygdala.

Hippocampal mossy fibers and radial-maze learning in the mouse: a correlation with spatial working memory but not with non-spatial reference memory.

One hundred and eight male mice from nine different inbred strains were tested for two aspects of learning in an eight-arm radial maze. In the first experimental arrangement of the maze, measuring spatial working memory, clear strain differences were found on the fifth day of training. Furthermore, this type of learning showed a high positive correlation with the size of the intra- and infrapyramidal hippocampal mossy fiber terminal field as revealed with Timm's staining. In the second experiment, in which non-spatial reference memory was tested, significant strain differences were found for the learning variables, but there were no significant covariations with the sizes of the intra- and infrapyramidal mossy fiber terminal fields. These results, combined with previous data, suggest that heritable variations of the hippocampal intra- and infrapyramidal mossy fiber projection influence processes determining spatial learning capabilities in mice.

Neonatal thyroxine treatment: changes in the number of corticotropin-releasing-factor (CRF) and neuropeptide Y (NPY) containing neurons and density of tyrosine hydroxylase positive fibers (TH) in the amygdala correlate with anxiety-related behavior of wistar rats.

Neonatal hyperthyroidism induces persisting alterations in the adult brain, e.g. in spatial learning and hippocampal morphology. In the present study, the relationship between anxiety-related behavior and amygdala morphology was investigated in the adult rat after transient neonatal hyperthyroidism (daily s.c. injections of 7.5 microg L-thyroxine in 0.5 ml 0.9% NaCl solution from postnatal day p1 to p12). The behavioral tests used to study anxiety-related behavior were the motility test, elevated plus-maze and fear-sensitized acoustic startle response. In the amygdala, the number of neurons containing the anxiogenic peptide corticotropin releasing factor (CRF-ir and CRF mRNA) and anxiolytic neuropeptide Y (NPY-ir), the total number of neurons and the density of tyrosine hydroxylase immunoreactive (TH-ir) fibers were quantified. Thyroxine-treated pups presented an accelerated development including opening of eyes and snout elongation as typical signs of hyperthyroidism. Thyroxine-treated adult animals displayed a reduced anxiety in the motility box and elevated plus maze, a reduction in the number of CRF-ir neurons in the central nucleus of the amygdala, as well as an increase in the number of NPY-ir neurons and density of TH-ir fibers in nuclei of the basolateral complex of the amygdala. Moreover, there was a reduction in the total number of neurons in all nuclei of the basolateral complex (despite the higher number of NPY-ir neurons), but not central nucleus of the amygdala. The number of CRF-ir neurons in the central nucleus correlated positively with anxiety-related behavior, and the number of NPY-ir neurons and the density of TH-ir fibers in the basolateral complex correlated inversely with anxiety-related behavior. The findings suggested a shift toward an anxiolytic rather than anxiogenic distribution of peptidergic neurons and fibers in the amygdala at adult age following transient neonatal hyperthyroidism.

Proliferation and differentiation of glial fibrillary acidic protein-immunoreactive glial cells in organotypic slice cultures of rat hippocampus.

The present paper deals with the proliferation and differentiation of glial cells in organotypic slice cultures of the rat hippocampal formation. Transverse slices of hippocampus of newborn to five-day-old rats were cultivated using the roller tube technique. To study the development of glial cells under these conditions, the slice cultures were processed for immunostaining employing antibodies against the glial fibrillary acidic protein. The proliferation of glial cells was studied in double-labeling experiments employing glial fibrillary acidic protein-immunostaining and the bromodeoxyuridine technique. The three-dimensional glial scaffold in the cultures was analysed in semithin and ultrathin cross-sections through the slice cultures after varying periods following explanation. Our results can be summarized as follows: 1. At all intervals after explanation of the slices there are numerous glial fibrillary acidic protein-positive cells with morphological characteristics of astrocytes. 2. With some modifications, the differentiation of astrocytes and their processes follows similar rules as observed in the hippocampus in vivo. A radial glial scaffold is also formed in the cultures. However, in cultures, a regular pattern of radial fibers is more obvious in the hippocampus proper than in the dentate gyrus. This glial scaffold persists after 20 days in vitro whereas it is known to disappear after the first postnatal week in vivo. 3. Bromodeoxyuridine-positive nuclei of glial cells were found at all time periods after explanation. After short incubation periods, they were most frequent in the "ventricular" zones of the cultures. Following longer incubation periods after bromodeoxyuridine administration, proliferating cells were found throughout the cultures, covering and underlying the cultured tissue. A rim of laterally migrating astrocytes completely surrounds the cultures. Our results demonstrate that glial cells proliferate and differentiate under the present culture conditions. After three weeks of incubation the whole slice culture is surrounded by a glial cover which may play an important role for the survival and differentiation of the cultured hippocampal neurons.

Neuroleptics ameliorate phencyclidine-induced impairments of short-term memory.

1. Phencyclidine (PCP), a non-competitive NMDA-receptor antagonist, is able to induce schizophrenia-like symptoms in animals and in humans. It is known that schizophrenic patients have deficits in memory processes. 2. Therefore, it was investigated whether subchronic pulsatile or continuous application of 5.0 mg kg(-1) PCP over 5 days induce short-term memory deficits in holeboard learning and the action of two different neuroleptics on this behavioural test. 3. First, an impairment in the holeboard task was described when the animals were tested 24 h after the last application but not after 15 min or 1 h after the last injection. Secondly, the influence of haloperidol and risperidone on the PCP-induced short-term memory changes was tested. 4. The combined application of PCP and risperidone led to a complete antagonism of the short-term deficits, but the combined treatment with haloperidol was accompanied by a partial abolishment of the PCP-induced deficits. 5. PCP led to an upregulation of the glutamate binding sites in striatum and nucleus accumbens whereas the D(2) binding sites were reduced in striatum. The D(1) binding sites seem to be unchanged. The receptor protein expression of glutamate receptors mGluR1, GluR2, GluR5/7 and NMDAR1 were not modified in response to PCP treatment. 6. The determination of a subpopulation of GABAergic interneurons shows a decrease of the cells within the CA3 of the hippocampal formation. 7. These findings indicate that PCP induced impairments in short term memory can be detected by holeboard learning and may provide an interesting tool for the search of new neuroleptics.

Plasticity of identified neurons in slice cultures of hippocampus: a combined Golgi/electron microscopic and immunocytochemical study.

The combined Golgi/electron microscope (EM) technique and immunocytochemistry for glutamate decarboxylase (GAD) were used to study the differentiation of pyramidal neurons and GABAergic inhibitory non-pyramidal cells in slice cultures of rat and mouse hippocampus. Golgi-impregnated and gold-toned cultures showed the characteristic curved structure of the Ammon's horn. Hippocampal regions CA1, CA3 and fascia dentata could easily be recognized. Pyramidal neurons in CA1 displayed all characteristics of this cell type known from Golgi studies in situ. A triangular cell body gives rise to a main apical dendritic shaft which gives off several side branches. Basal dendrites and the axon originate at the basal pole of the cell body. Apical and basal dendrites are densely covered with spines. As a characteristic feature of the cultured pyramidal cells, numerous spines were observed on the cell body. Most likely due to flattening of the slice during incubation, the pyramidal neurons in CA1 are no longer arranged in a densely packed layer. This results in more space between cell bodies which is filled in by numerous horizontal and basal dendrites originating from the pyramidal cell perikaryon. CA1 pyramidal neurons in slice cultures of the rat or mouse thus resemble the pyramidal neurons in the CA1 region of the primate hippocampus where a similar loose distribution of cell bodies is found. In the electron microscope, cell bodies and dendritic shafts of the gold-toned pyramidal cells formed symmetric synaptic contacts with presynaptic terminals. Numerous boutons were observed that established asymmetric synaptic contacts on gold-toned spines of peripheral pyramidal cell dendrites. This suggests that considerable synaptic reorganization takes place because in situ spines on peripheral dendritic segments are contacted mainly by extrinsic afferents. Like in situ, at least some of the terminals that establish symmetric synaptic contacts are GABAergic. In our immunocytochemical study we observed numerous GAD-positive terminals that formed a dense pericellular plexus around immunonegative cell bodies of pyramidal neurons. In the electron microscope these structures were identified as presynaptic boutons which formed symmetric synaptic contacts on cell bodies and dendritic shafts. They most likely originated from the GAD-positive neurons scattered in all layers of the slice culture. Our results have shown that the main cell types in the hippocampus, pyramidal neurons and GABAergic inhibitory non-pyramidal cells, survive and differentiate under the present culture conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Short-term down-regulation of the brain-specific, PtdIns(3,4,5)P3/Ins(1,3,4,5)P4-binding, adapter protein, p42IP4/centaurin-alpha 1 in rat brain after acoustic and electric stimulation.

The protein p42(IP4), expressed mainly in brain, specifically recognizes two second messenger molecules, Ins(1,3,4,5)P(4) (IP(4)), a water soluble metabolite of IP(3) and the lipid PtdIns(3,4,5)P(3) (PIP(3)), the product of the growth factor-activated enzyme PI-3-kinase. Here, we studied whether there is short-term regulation of the expression level of p42(IP4) in limbic brain areas following acoustic and electric stimulation. The stimuli down-regulated the mRNA and protein levels within 2h in amygdala, hypothalamus and cingulate/retrospenial cortex. p42(IP4) mRNA decreased by about 50% for about 24h, but recovered to control values after 72 h. The present results are the first indication of a specific role of p42(IP4) in the short-term regulation of a behavioral response. They indicate that p42(IP4), an adapter protein in PIP(3)-dependent cellular signaling, may play an important role in the signal transduction pathways regulating plasticity in neuronal cells.

Hippocampal mossy fiber distribution covaries with open-field habituation in the mouse.

We studied the sizes of the hippocampal intra- and infrapyramidal mossy fiber (iip-MF) terminal fields and habituation to a new environment (open-field) in 25 genetically different groups of mice. Based on previous findings and theoretical considerations, a positive relationship between the size of the iip-MF terminal fields and the extent of behavioral change between two subsequent exposures to the open-field was expected. In fact, such a relationship was revealed by a factor analysis. Our results indicate that mice possessing large iip-MF terminal fields are more efficient in the processing of spatial information.

Dissociation of spatial reference memory, spatial working memory, and hippocampal mossy fiber distribution in two rat strains differing in emotionality.

Rats of the inbred strains DA/Han and BDE/Han were compared on two complex spatial learning tasks, a spatial reference memory task in a 16-unit multiple T-maze and a spatial working memory task in an eight-arm radial-maze. In addition, sizes of hippocampal mossy fiber terminal fields were measured. BDE rats showed marked superiority in multiple T-maze learning whereas DA rats outperformed BDE rats on the radial-maze task. DA rats had significantly larger intra- and infrapyramidal mossy fiber terminal fields (IIP-MF). This is consistent with findings from other studies suggesting that large IIP-MF are related to excellent spatial radial-maze learning, but it also indicates that size of IIP-MF is correlated with processing of a specific type of spatial information rather than with overall spatial abilities. BDE rats had more extended suprapyramidal mossy fiber projections (SP-MF) and a larger hilus. Rats of both strains differed in exploratory behaviour and emotionality: DA rats revealed little freezing and had a high rearing activity, whereas BDE rats showed frequent freezing and reared rarely. Results suggest that IIP-MF are involved with flexible expression of memory, updating environmental information and parallel processing whereas SP-MF might be linked to processing of familiar information. Presumably, emotional factors contribute to performance differences.