Significance of Input Correlations in Striatal Function

The striatum is the main input station of the basal ganglia and is strongly associated with motor and cognitive functions. Anatomical evidence suggests that individual striatal neurons are unlikely to share their inputs from the cortex. Using a biologically realistic large-scale network model of striatum and cortico-striatal projections, we provide a functional interpretation of the special anatomical structure of these projections. Specifically, we show that weak pairwise correlation within the pool of inputs to individual striatal neurons enhances the saliency of signal representation in the striatum. By contrast, correlations among the input pools of different striatal neurons render the signal representation less distinct from background activity. We suggest that for the network architecture of the striatum, there is a preferred cortico-striatal input configuration for optimal signal representation. It is further enhanced by the low-rate asynchronous background activity in striatum, supported by the balance between feedforward and feedback inhibitions in the striatal network. Thus, an appropriate combination of rates and correlations in the striatal input sets the stage for action selection presumably implemented in the basal ganglia

Hybrid inorganic-organic composite nanoparticles from crosslinkable polyfluorenes

Polyfluorenes with pendant alkoxysilyl groups have been used to prepare inorganic–organic composite nanoparticles (diameter = 80–220 nm) in which the conjugated polymer is dispersed within a silica matrix. Preparation of these nanoparticles is achieved by simultaneous nanoprecipitation of the conjugated polymer and hydrolysis/crosslinking of the alkoxysilyl groups under basic conditions. The composition of the nanocomposites is controlled by addition of an alkoxysilane monomer, tetramethylorthosilicate. The hybrid nanoparticles form highly stable dispersions in water and buffer (pH 9.2). The size of the nanoparticles can be tuned by varying the amount of the alkoxysilane monomer added during the nanoprecipitation process. Increasing the relative amount of alkoxysilane monomer also increases the proportion of polyfluorene chains that adopt the higher energy β-phase conformation within the resultant nanoparticles. Nanoparticles with the highest silica content were found to have increased photoluminescence quantum yields. This work provides a controllable method for optimisation of the photophysical properties of light-emitting conjugated polymer nanoparticles via a simple aqueous processing technique

Intermittent Stimulation of the Nucleus Basalis of Meynert Improves Working Memory in Adult Monkeys

Acetylcholine in the neocortex is critical for executive function [1-3]. Degeneration of cholinergic neurons in aging and Alzheimers dementia is commonly treated with cholinesterase inhibitors [4-7]; however, these are modestly effective and are associated with side effects that preclude effective dosing in many patients [8]. Electrical activation of the nucleus basalis (NB) of Meynert, the source of neocortical acetylcholine [9, 10], provides a potential method of improving cholinergic activation [11, 12]. Here we tested whether NB stimulation would improve performance of a working memory task in a nonhuman primate model. Unexpectedly, intermittent stimulation proved to be most beneficial (60 pulses per second, for 20 s every minute), whereas continuous stimulation often impaired performance. Pharmacological experiments confirmed that the effects depended on cholinergic activation. Donepezil, a cholinesterase inhibitor, restored performance in animals impaired by continuous stimulation but did not improve performance further during intermittent stimulation. Intermittent stimulation was rendered ineffective by either nicotinic or muscarinic receptor antagonists. In the months after stimulation began, performance also improved in sessions without stimulation. Our results reveal that intermittent NB stimulation can improve working memory, a finding that has implications for restoring cognitive function in aging and Alzheimers dementia

Scalable synthesis of multicolour conjugated polymer nanoparticles via Suzuki-Miyaura polymerisation in a miniemulsion and application in bioimaging.

Suzuki cross-coupling polymerisation of aryldibromides and aryldiboronate esters in a sodium dodecyl sulfate (SDS)-stabilised miniemulsion provides a versatile and direct route to fluorescent conjugated polymer nanoparticles (CPNs). These nanoparticles have a conjugated backbone based on poly(9,9-dioctylfluorene) (PFO), however, significant structural diversity is introduced by incorporation of electron withdrawing, heterocyclic comonomers (5–50 mol.%) in order to tune the emission wavelengths from blue to far-red/near-infrared. The robust nature of the polymerisation methodology allows for rapid assessment of the relationship between polymer composition, chain morphology and optical properties of the resultant CPNs. Moreover, the CPNs (after a simple and rapid purification step) can be used directly in fluorescence-based intracellular labelling experiments (in HCT116 cells), in which they display low cytotoxicity at biologically-useful concentrations

Fluorescent nanoparticles from PEGylated polyfluorenes

Polyfluorenes with both alkyl and poly(ethylene glycol) (PEG) side-chains have been synthesised and processed into fluorescent nanoparticles via nanoprecipitation. The PEG/alkyl ratio is found to exert a significant influence over the size, polymer microstructure and optical properties of the resultant nanoparticles. This paves the way for a deeper understanding of how polymer structure can be manipulated to provide greater control over the nanoprecipitation process

Synthesis and evaluation of resins bearing substrate-like inhibitor functions for capturing copper amine oxidases

none6In order to make new tools available for investigating interactions between enzyme and substrate-like inhibitors in copper amine oxidases (CAOs), a class of enzymes that controls important cellular processes such as the crosslinking of elastin and collagen, cell proliferation and the regulation of intracellular polyamines, starting from a previous work we synthesized the poly(N,N-dimethylacrylamide)-based resin R2 and the new TentaGel resins T3 and T4 obtained by immobilizing onto commercial TentaGel S-Br properly designed CAO substrate-like inhibitor moieties. The anchoring of CAO substrate-like inhibitor moieties was carried out through stable ether bonds onto commercial TentaGel S-Br which contains bromomethyl groups susceptible to nucleophilic substitution reactions. We resorted to polyacrylamide gel electrophoresis (PAGE) experiments to ascertain the capability of the prepared resins to capture plasma amine oxidase (PAO) and diamine oxidase (DAO), members of the CAO family. The poly(N,N-dimethylacrylamide)-based resin R2 resulted able of blocking PAO and DAO being the first insoluble polymeric materials able to capture enzymes of the CAO family.Pocci M; Alfei S; Castellaro S; Lucchesini F; Milanese M; Bertini V.Pocci, Marco; Alfei, Silvana; Castellaro, Sara; Lucchesini, Francesco; Milanese, Marco; Bertini, Vincenz