Reduction in neuronal L-type calcium channel activity in a double knock-in mouse model of Alzheimer's disease

Increased function of neuronal L-type voltage-sensitive Ca^2 + channels (L-VSCCs) is strongly linked to impaired memory and altered hippocampal synaptic plasticity in aged rats. However, no studies have directly assessed L-VSCC function in any of the common mouse models of Alzheimer's disease where neurologic deficits are typically more robust. Here, we used cell-attached patch-clamp recording techniques to measure L-VSCC activity in CA1 pyramidal neurons of partially dissociated hippocampal “zipper” slices prepared from 14-month-old wild-type mice and memory-impaired APP/PS1 double knock-in mice. Surprisingly, the functional channel density of L-VSCCs was significantly reduced in the APP/PS1 group. No differences in voltage dependency and unitary conductance of L-VSCCs were observed. The results suggest that mechanisms for Ca^2 + dysregulation can differ substantially between animal models of normal aging and models of pathological aging.     

Leisure activities, cognition and dementia

Accumulated evidence shows that leisure activities have a positive impact on cognitive function and dementia. This review aimed to systematically summarize the current evidence on this topic taking into account the limitations of the studies and biological plausibility for the underlying mechanisms linking cognition, dementia and leisure activities, with special attention on mental, physical and social activities. We included only longitudinal studies, with a follow-up time of at least 2 years, published in English from 1991 to March 2011 on leisure activities and cognition (n = 29) or dementia (n = 23) and provided some evidence from intervention studies on the topic. A protective effect of mental activity on cognitive function has been consistently reported in both observational and interventional studies. The association of mental activity with the risk of dementia was robust in observational studies but inconsistent in clinical trials. The protective effect of physical activity on the risk of cognitive decline and dementia has been reported in most observational studies, but has been less evident in interventional studies. Current evidence concerning the beneficial effect of other types of leisure activities on the risk of dementia is still limited and results are inconsistent. For future studies it is imperative that the assessment of leisure activities is standardized, for example, the frequency, intensity, duration and the type of activity; and also that the cognitive test batteries and the definition of cognitive decline are harmonized/standardized. Further, well designed studies with long follow-up times are necessary. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.     

Hierarchical Categorical Perception in Sensing and Cognitive Processes

This article considers categorical perception (CP) as a crucial process involved in all sort of communication throughout the biological hierarchy, i.e. in all of biosemiosis. Until now, there has been consideration of CP exclusively within the functional cycle of perception–cognition–action and it has not been considered the possibility to extend this kind of phenomena to the mere physiological level. To generalise the notion of CP in this sense, I have proposed to distinguish between categorical perception (CP) and categorical sensing (CS) in order to extend the CP framework to all communication processes in living systems, including intracellular, intercellular, metabolic, physiological, cognitive and ecological levels. The main idea is to provide an account that considers the heterarchical embeddedness of many instances of CP and CS. This will take me to relate the hierarchical nature of categorical sensing and perception with the equally hierarchical issues of the “binding problem”, “triadic causality”, the “emergent interpretant” and the increasing semiotic freedom observed in biological and cognitive systems.

Targeted disruption of the Pak5 and Pak6 genes in mice leads to deficits in learning and locomotion

PAK6 is a member of the group B family of PAK serine/threonine kinases, and is highly expressed in the brain. The group B PAKs, including PAK4, PAK5, and PAK6, were first identified as effector proteins for the Rho GTPase Cdc42. They have important roles in filopodia formation, the extension of neurons, and cell survival. Pak4 knockout mice die in utero, and the embryos have several abnormalities, including a defect in the development of motor neurons. In contrast, Pak5 knockout mice do not have any noticeable abnormalities. So far nothing is known about the biological function of Pak6. To address this, we have deleted the Pak6 gene in mice. Since Pak6 and Pak5 are both expressed in the brain, we also generated Pak5/Pak6 double knockout mice. These mice were viable and fertile, but had several locomotor and behavioral deficits. Our results indicate that Pak5 and Pak6 together are not required for viability, but are required for a normal level of locomotion and activity as well as for learning and memory. This is consistent with a role for the group B PAKs in the nervous system.     

The Cognitive Enhancer SGS742 Does not Involve Major Known Signaling Cascades in OF1 Mice

In a previous study we have shown that SGS742, a cognitive enhancer acting by GABA(B) receptor antagonism improved spatial learning in OF1 mice. The aim of the study was therefore to screen representatives of several signaling cascades known to be involved in memory formation at the protein level. NaCl-, SGS742- treatment and yoked controls for NaCl and SGS742 were studied. Six hours following testing OF1 mice in the Morris water maze, hippocampal signaling proteins calmodulin kinase II (CaMKII) (phosphorylated (P) and non-phosphorylated (NP) form), CREB (P, NP), ERK (P, NP), BDNF, Egr-1, Trk-B and neuro-cytoskeleton elements drebrin and PSD-95 were determined by immunoblotting. Protein patterns were comparable between the control and SGS742 treated group revealing that these proteins may not be involved in the mechanisms underlying cognitive enhancement by SGS742 and this should be taken into account for interpretation and design of previous and future related neurochemical studies.     

On the role of emotion in biological and robotic autonomy

This paper reviews some of the differences between notions of biological and robotic autonomy, and how these differences have been reflected in discussions of embodiment, grounding and other concepts in AI and autonomous robotics. Furthermore, the relations between homeostasis, emotion and embodied cognition are discussed as well as recent proposals to model their interplay in robots, which reflects a commitment to a multi-tiered affectively/emotionally embodied view of mind that takes organismic embodiment more serious than usually done in biologically inspired robotics.     

Evolution,altruism and cognitive architecture: a critique of Sober and Wilson’s argument for psychological altruism

Sober and Wilson have propose a cluster of arguments for the conclusion that “natural selection is unlikely to have given us purely egoistic motives” and thus that psychological altruism is true. I maintain that none of these arguments is convincing. However, the most powerful of their arguments raises deep issues about what egoists and altruists are claiming and about the assumptions they make concerning the cognitive architecture underlying human motivation.     

Meaning in Nature: Organic Manufacture?

The paper examines Marcello Barbieri’s (2007) Introduction to Biosemiotics. Highlighting debate within the biosemiotic community, it focuses on what the volume offers to those who explain human intellect in relation to what Turing called our ‘physical powers.’ In scrutinising the basis of world-modelling, parallels and contrasts are drawn with other work on embodied-embedded cognition. Models dominate biology. Is this a qualitative fact or does it point to biomechanisms? In evaluating the 18 contributions, it is suggested that the answers will shape the field. First, they will decide if biochemistry and explanatory reduction can be synergised by biosemantics. Second, they will show if our intellectual powers arise from biology. Does thinking use—not a language faculty—but what Marko? and colleagues call semiosis by the living? Resolution of such issues, it is suggested, can change how we view cognition. Above all, if the biomechanists win the day, cultural models can be regarded as extending natural meaning. On such a view, biomechanisms prompt us to act and perceive as we model our own natural models. This fits Craik’s vision: intellect gives us the alphanumerical ‘symbols’ that allow thoughts to have objective validity. For the biomechanist, this is explained—not by brains alone—but, rather, by acting under the constraints of historically extended sensoria.     

Design,synthesis and pharmacological evaluation of some novel indanone derivatives as acetylcholinesterase inhibitors for the management of cognitive dysfunction

The present study reports the effect of indanone derivatives on scopolamine induced deficit cholinergic neurotransmission serving as promising leads for the therapeutics of cognitive dysfunction. Eleven compounds 54–64 have been designed, synthesised and evaluated against behavioural alterations using step down passive avoidance protocol at a dose of 0.5?mg/kg with Donepezil (1) as the reference standard. All the synthesised compounds were evaluated for their in vitro acetylcholinesterase (AChE) inhibition at five different concentrations using mice brain homogenate as the source of the enzyme. Compounds 54, 56, 59 and 64 displayed appreciable activity with an IC₅₀ value of 14.06?µM, 12.30?µM, 14.06?µM and 12.01?µM, respectively towards acetylcholinesterase inhibition. The molecular docking study performed to predict the binding mode of the compounds suggested that these compounds could bind appreciably to the amino acids present at the active site of recombinant human acetylcholinesterase (rhAChE). The behavioural, biochemical and in silico pharmacokinetic studies were in concordance with each other.     

Every rose has its thorn: Infants' responses to pointed shapes in naturalistic contexts

Plants produce dangerous chemical and physical defenses that have shaped the physiology and behavior of the herbivorous predators that feed on them. Here we explore the impact that these plant defenses may have had on humans by testing infants' responses to plants with and without sharp-looking thorns. To do this, we presented 8- to 18-month-olds with plants and control stimuli and measured their initial reaching behavior and subsequent object exploration behavior. Half of the stimuli had sharp-looking thorns or pointed parts while the other half did not. We found that infants exhibited both an initial reluctance to touch and minimized subsequent physical contact with plants compared to other object types. Further, infants treated all plants as potentially dangerous, whether or not they possessed sharp-looking thorns. These results reveal novel dimensions of a behavioral avoidance strategy in infancy that would mitigate potential harm from plants.