Ultrastructural Correlates of Presynaptic Functional Heterogeneity in Hippocampal Synapses

1. Download : Download high-res image (218KB)
2. Download : Download full-size image

     

Behavioral Correlates of Primates Conservation Status: Intrinsic Vulnerability to Anthropogenic Threats

Behavioral traits are likely to influence species vulnerability to anthropogenic threats and in consequence, their risk of extinction. Several studies have addressed this question and have highlighted a correlation between reproductive strategies and different viability proxies, such as introduction success and local extinction risk. Yet, very few studies have investigated the effective impact of social behaviour, and evidence regarding global extinction risk remains scant. Here we examined the effects of three main behavioral factors: the group size, the social and reproductive system, and the strength of sexual selection on global extinction risk. Using Primates as biological model, we performed comparative analysis on 93 species. The conservation status as described by the IUCN Red List was considered as a proxy for extinction risk. In addition, we added previously identified intrinsic factors of vulnerability to extinction, and a measure of the strength of the human impact for each species, described by the human footprint. Our analysis highlighted a significant effect of two of the three studied behavioral traits, group size and social and reproductive system. Extinction risk is negatively correlated with mean group size, which may be due to an Allee effect resulting from the difficulties for solitary and monogamous species to find a partner at low densities. Our results also indicate that species with a flexible mating system are less vulnerable. Taking into account these behavioral variables is thus of high importance when establishing conservation plans, particularly when assessing species relative vulnerability.     

Loss of Hippocampal Neurons after Kainate Treatment Correlates with Behavioral Deficits

Treating rats with kainic acid induces status epilepticus (SE) and leads to the development of behavioral deficits and spontaneous recurrent seizures later in life. However, in a subset of rats, kainic acid treatment does not induce overt behaviorally obvious acute SE. The goal of this study was to compare the neuroanatomical and behavioral changes induced by kainate in rats that developed convulsive SE to those who did not. Adult male Wistar rats were treated with kainic acid and tested behaviorally 5 months later. Rats that had experienced convulsive SE showed impaired performance on the spatial water maze and passive avoidance tasks, and on the context and tone retention tests following fear conditioning. In addition, they exhibited less anxiety-like behaviors than controls on the open-field and elevated plus-maze tests. Histologically, convulsive SE was associated with marked neuron loss in the hippocampal CA3 and CA1 fields, and in the dentate hilus. Rats that had not experienced convulsive SE after kainate treatment showed less severe, but significant impairments on the spatial water maze and passive avoidance tasks. These rats had fewer neurons than control rats in the dentate hilus, but not in the hippocampal CA3 and CA1 fields. Correlational analyses revealed significant relationships between spatial memory indices of rats and neuronal numbers in the dentate hilus and CA3 pyramidal field. These results show that a part of the animals that do not display intense behavioral seizures (convulsive SE) immediately after an epileptogenic treatment, later in life, they may still have noticeable structural and functional changes in the brain.     

Cortical and Hippocampal Correlates of Deliberation during Model-Based Decisions for Rewards in Humans

How do we use our memories of the past to guide decisions we''ve never had to make before? Although extensive work describes how the brain learns to repeat rewarded actions, decisions can also be influenced by associations between stimuli or events not directly involving reward — such as when planning routes using a cognitive map or chess moves using predicted countermoves — and these sorts of associations are critical when deciding among novel options. This process is known as model-based decision making. While the learning of environmental relations that might support model-based decisions is well studied, and separately this sort of information has been inferred to impact decisions, there is little evidence concerning the full cycle by which such associations are acquired and drive choices. Of particular interest is whether decisions are directly supported by the same mnemonic systems characterized for relational learning more generally, or instead rely on other, specialized representations. Here, building on our previous work, which isolated dual representations underlying sequential predictive learning, we directly demonstrate that one such representation, encoded by the hippocampal memory system and adjacent cortical structures, supports goal-directed decisions. Using interleaved learning and decision tasks, we monitor predictive learning directly and also trace its influence on decisions for reward. We quantitatively compare the learning processes underlying multiple behavioral and fMRI observables using computational model fits. Across both tasks, a quantitatively consistent learning process explains reaction times, choices, and both expectation- and surprise-related neural activity. The same hippocampal and ventral stream regions engaged in anticipating stimuli during learning are also engaged in proportion to the difficulty of decisions. These results support a role for predictive associations learned by the hippocampal memory system to be recalled during choice formation.     

Neuronal and Astroglial Correlates Underlying Spatiotemporal Intrinsic Optical Signal in the Rat Hippocampal Slice

Widely used for mapping afferent activated brain areas in vivo, the label-free intrinsic optical signal (IOS) is mainly ascribed to blood volume changes subsequent to glial glutamate uptake. By contrast, IOS imaged in vitro is generally attributed to neuronal and glial cell swelling, however the relative contribution of different cell types and molecular players remained largely unknown. We characterized IOS to Schaffer collateral stimulation in the rat hippocampal slice using a 464-element photodiode-array device that enables IOS monitoring at 0.6 ms time-resolution in combination with simultaneous field potential recordings. We used brief half-maximal stimuli by applying a medium intensity 50 Volt-stimulus train within 50 ms (20 Hz). IOS was primarily observed in the str. pyramidale and proximal region of the str. radiatum of the hippocampus. It was eliminated by tetrodotoxin blockade of voltage-gated Na⁺ channels and was significantly enhanced by suppressing inhibitory signaling with gamma-aminobutyric acid(A) receptor antagonist picrotoxin. We found that IOS was predominantly initiated by postsynaptic Glu receptor activation and progressed by the activation of astroglial Glu transporters and Mg²⁺-independent astroglial N-methyl-D-aspartate receptors. Under control conditions, role for neuronal K⁺/Cl⁻ cotransporter KCC2, but not for glial Na⁺/K⁺/Cl⁻ cotransporter NKCC1 was observed. Slight enhancement and inhibition of IOS through non-specific Cl⁻ and volume-regulated anion channels, respectively, were also depicted. High-frequency IOS imaging, evoked by brief afferent stimulation in brain slices provide a new paradigm for studying mechanisms underlying IOS genesis. Major players disclosed this way imply that spatiotemporal IOS reflects glutamatergic neuronal activation and astroglial response, as observed within the hippocampus. Our model may help to better interpret in vivo IOS and support diagnosis in the future.     

Correlation Between Electroencephalogram Isoelectric Time and Hippocampal Norepinephrine Levels, Measured by Microdialysis, During Ischemia in Rats

It is suggested that norepinephrine (NE) plays a role during transient forebrain ischemia. NE may have a protective action against neuronal cell death in the hippocampus, or it may be one of the causes of injurious ischemic effects. We used the microdialysis technique to study extracellular NE levels in the rat hippocampus before, during, and after 30 min of transient incomplete forebrain ischemia (induced by four-vessel occlusion) to describe the time course of NE in this condition. There was a maximal increase (fivefold) in extracellular NE after 10 min of reflow only when the electroencephalogram was isoelectric. NE levels returned to baseline 40 min after release of the carotid clamps and remained constant for the next 80 min. Thus there appears to be a transient NE overflow in the hippocampus during ischemia, closely related to the complete loss of brain electrical activity.     

Neural Correlates of Task Cost for Stance Control with an Additional Motor Task: Phase-Locked Electroencephalogram Responses

With appropriate reallocation of central resources, the ability to maintain an erect posture is not necessarily degraded by a concurrent motor task. This study investigated the neural control of a particular postural-suprapostural procedure involving brain mechanisms to solve crosstalk between posture and motor subtasks. Participants completed a single posture task and a dual-task while concurrently conducting force-matching and maintaining a tilted stabilometer stance at a target angle. Stabilometer movements and event-related potentials (ERPs) were recorded. The added force-matching task increased the irregularity of postural response rather than the size of postural response prior to force-matching. In addition, the added force-matching task during stabilometer stance led to marked topographic ERP modulation, with greater P2 positivity in the frontal and sensorimotor-parietal areas of the N1-P2 transitional phase and in the sensorimotor-parietal area of the late P2 phase. The time-frequency distribution of the ERP primary principal component revealed that the dual-task condition manifested more pronounced delta (1–4 Hz) and beta (13–35 Hz) synchronizations but suppressed theta activity (4–8 Hz) before force-matching. The dual-task condition also manifested coherent fronto-parietal delta activity in the P2 period. In addition to a decrease in postural regularity, this study reveals spatio-temporal and temporal-spectral reorganizations of ERPs in the fronto-sensorimotor-parietal network due to the added suprapostural motor task. For a particular set of postural-suprapostural task, the behavior and neural data suggest a facilitatory role of autonomous postural response and central resource expansion with increasing interregional interactions for task-shift and planning the motor-suprapostural task.     

Hippocampal Synaptic Expansion Induced by Spatial Experience in Rats Correlates with Improved Information Processing in the Hippocampus

Spatial water maze (WM) overtraining induces hippocampal mossy fiber (MF) expansion, and it has been suggested that spatial pattern separation depends on the MF pathway. We hypothesized that WM experience inducing MF expansion in rats would improve spatial pattern separation in the hippocampal network. We first tested this by using the the delayed non-matching to place task (DNMP), in animals that had been previously trained on the water maze (WM) and found that these animals, as well as animals treated as swim controls (SC), performed better than home cage control animals the DNMP task. The “catFISH” imaging method provided neurophysiological evidence that hippocampal pattern separation improved in animals treated as SC, and this improvement was even clearer in animals that experienced the WM training. Moreover, these behavioral treatments also enhance network reliability and improve partial pattern separation in CA1 and pattern completion in CA3. By measuring the area occupied by synaptophysin staining in both the stratum oriens and the stratun lucidum of the distal CA3, we found evidence of structural synaptic plasticity that likely includes MF expansion. Finally, the measures of hippocampal network coding obtained with catFISH correlate significantly with the increased density of synaptophysin staining, strongly suggesting that structural synaptic plasticity in the hippocampus induced by the WM and SC experience is related to the improvement of spatial information processing in the hippocampus.     

Electroencephalogram structure

The representation of an electroencephalogram as a convolution of harmonic functions having negative decrements with discrete (evenly discontinuous) white Gaussian noise was considered. A substantiation of this representation is given. It was numerically shown that the convolution of the decrement damping alpha-rhythm of one frequency with discrete white noise is a narrow-band chaos, an irregular spindle-shaped activity, which results in the appearance of close spectral components in the spectrum of power. The estimation of the autocorrelation function represented a damping cosinusoid shifted in phase depending of the factor of fading. The absolute value of convolution described an envelope of the output signal. The average duration of spindles decreased as the module of the decrement increased.     

Micro-MRI Study of Cerebral Aging: Ex Vivo Detection of Hippocampal Subfield Reorganization,Microhemorrhages and Amyloid Plaques in Mouse Lemur Primates

Mouse lemurs are non-human primate models of cerebral aging and neurodegeneration. Much smaller than other primates, they recapitulate numerous features of human brain aging, including progressive cerebral atrophy and correlation between regional atrophy and cognitive impairments. Characterization of brain atrophy in mouse lemurs has been done by MRI measures of regional CSF volume and by MRI measures of regional atrophy. Here, we further characterize mouse lemur brain aging using ex vivo MR microscopy (31 µm in-plane resolution). First, we performed a non-biased, direct volumetric quantification of dentate gyrus and extended Ammon''s horn. We show that both dentate gyrus and Ammon''s horn undergo an age-related reorganization leading to a growth of the dentate gyrus and an atrophy of the Ammon''s horn, even in the absence of global hippocampal atrophy. Second, on these first MR microscopic images of the mouse lemur brain, we depicted cortical and hippocampal hypointense spots. We demonstrated that their incidence increases with aging and that they correspond either to amyloid deposits or to cerebral microhemorrhages.     

Infant socialization in Primates

This review considers evolutionary trends, functions, stages, and current issues in Primate socialization. The concept of social “set” is discussed in the context of the interactional nature of socialization, where the infant is regarded as a primary effector in its own socialization. Laboratory approaches and measurement techniques are reviewed briefly.     

Prolactin Synthesis in Primates

THERE is compelling physiological evidence that prolactin and growth hormone in primates are separate proteins, but no conclusive chemical evidence has been obtained in support of this¹. Indeed the close similarity in the primary structure of human pituitary growth hormone (HGH) and ovine pituitary lactogenic hormone² has reinforced the view that perhaps, in the human, lactation and growth are controlled by a single pituitary protein. Histological and immunofluorescence studies using antiserum to ovine prolactin (AOP)³ have shown, however, that there is a substance in primate pituitaries which is immunochemically related to ovine prolactin (OP) and distinguishable from growth hormone.