The NeuroBel: A Screening Test for Verbal Language Impairment in Spanish-Speaking Elderly People With Cognitive Decline.

PURPOSE: The NeuroBel is a short test that can detect cognitive decline using language tasks. This study replicated previous research using larger clinical samples from three Spanish-speaking countries. METHOD: Eight tasks were used to analyze verbal language functioning using a psycholinguistic approach. A total of 232 elderly, monolingual Spanish speakers from Spain, Cuba, and Colombia participated in this study. Of these, 76 had Alzheimer's disease (AD) in the initial phase, 75 had mild cognitive impairment (MCI), and 81 did not exhibit cognitive impairment (healthy controls). RESULTS: Significant differences were observed among the three clinical groups. The participants with AD and the participants with MCI had significantly lower NeuroBel scores than the control group on most of the tasks. However, repetition (in AD vs. MCI) and auditory lexical decision (in MCI vs. control) tasks were not significant in Tukey's post hoc tests. Discriminant analysis showed that 80.6% of the participants were correctly classified into the original groups and revealed the tasks that were the best and worst for differentiating among groups. The receiver-operating characteristic curves showed high sensitivity for AD and MCI. The area under the curve was .97 in the contrast of AD versus MCI + controls, .96 in the determination of overall cognitive decline (AD + MCI vs. controls), and .93 in the contrast of MCI and control groups. CONCLUSION: This study confirmed that the NeuroBel is a suitable test for detecting cognitive decline based on language impairment in Spanish-speaking elderly people.

KAT3-dependent acetylation of cell type-specific genes maintains neuronal identity in the adult mouse brain.

The lysine acetyltransferases type 3 (KAT3) family members CBP and p300 are important transcriptional co-activators, but their specific functions in adult post-mitotic neurons remain unclear. Here, we show that the combined elimination of both proteins in forebrain excitatory neurons of adult mice resulted in a rapidly progressing neurological phenotype associated with severe ataxia, dendritic retraction and reduced electrical activity. At the molecular level, we observed the downregulation of neuronal genes, as well as decreased H3K27 acetylation and pro-neural transcription factor binding at the promoters and enhancers of canonical neuronal genes. The combined deletion of CBP and p300 in hippocampal neurons resulted in the rapid loss of neuronal molecular identity without de- or transdifferentiation. Restoring CBP expression or lysine acetylation rescued neuronal-specific transcription in cultured neurons. Together, these experiments show that KAT3 proteins maintain the excitatory neuron identity through the regulation of histone acetylation at cell type-specific promoter and enhancer regions.

TherMouseDuino: An affordable Open-Source temperature control system for functional magnetic resonance imaging experimentation with mice.

INTRODUCTION: Functional magnetic resonance imaging (fMRI) is one of the most highly regarded techniques in the neuroimaging field. This technique is based on vascular responses to neuronal activation and is extensively used in clinical and animal research studies. In preclinical settings, fMRI is usually applied to anesthetized animals. However, anesthetics cause alterations, e.g. hypothermia, in the physiology of the animals and this has the potential to disrupt fMRI signals. The current temperature control method involves a technician, as well as monitoring the acquisition MRI sequences, also controlling the temperature of the animal; this is inefficient. METHODS: In order to avoid hypothermia in anesthetized rodents an Open-Source automatic temperature control device is presented. It takes signals from an intrarectal temperature sensor, as well as signals from a thermal bath, which warms up the body of the animal under study, in order to determine the mathematical model of the thermal response of the animal. RESULTS: A Proportional-Integral-Derivative (PID) algorithm, which was discretized in an Arduino microcontroller, was developed to automatically keep stable the body temperature of the animal under study. The PID algorithm has been shown to be accurate in preserving the body temperature of the animal. CONCLUSION: This work presents the TherMouseDuino. It is an Open-Source automatic temperature control system and reduces temperature fluctuations, thus providing robust conditions in which to perform fMRI experiments. Furthermore, our device frees up the technician to focus solely on monitoring the MRI sequences.

Extinction of the initial within-compound association established in a blocked preexposure to two compound flavours / Extinción de la asociación intracompuesto inicial establecida en una preexposición por bloques a dos compuestos de sabores

Extinction of the A↔X association after blocked preexposure to AX-BX was studied in two experiments. In Experiment 1, two groups of rats received long (14 trials) or short (4 trials) blocked preexposure to AX-BX and subsequent conditioning of X. The results showed that the AX association was equally preserved after long and short preexposure. Experiment 2 studied the effect of blocked preexposure to 0, 1 or 2 ruptures of the AX association on extinction. In this experiment a "rupture" is produced when, in subsequent blocks, one element of the original compound is presented in compound with a different element. A significant extinction was observed only when the AX association was broken twice

Se estudió la extinción de la asociación A↔X después de una preexposición por bloques a AX-BX en dos experimentos. En el Experimento 1, dos grupos de ratas recibieron una preexposición en bloques larga (14 ensayos) o corta (4 ensayos) a AX-BX y posteriormente se condicionó X. Los resultados mostraron que la asociación AX se preservó igualmente tanto después de la preexposición larga como de la corta. En el Experimento 2 se estudió el efecto de la preexposición por bloques a 0, 1 o 2 rupturas en la extinción de la asociación AX. En este experimento una "ruptura" se produce cuando, en los posteriores bloques, uno de los sabores que forman el compuesto inicial es presentado formando un compuesto con otro sabor diferente. Solo se observó una extinción significativa cuando la asociación AX se rompió dos veces

Preservation of within-compound associations after blocked preexposure to two compound flavors.

Three experiments investigated the extinction of the within-compound A↔X association established when two compound flavors, AX and BX, are preexposed in blocks (i.e., AX, AX, AX, ... BX, BX, BX). In Experiment 1, a group of rats received preexposure to a block of AX trials followed by a second block of BX trials (AX-BX), while a second group received blocked preexposure to the same stimuli in the opposite order (BX-AX). Subsequently, flavor A was paired with lithium chloride. This conditioning resulted in a similar reduction of consumption of flavor X in both groups. In Experiment 2 four groups of rats received blocked preexposure to AX-BX, AX-B, A-BX, or A-X. After aversive conditioning of X, consumption of A and B was significantly lower for the groups which received these flavors paired with X than for the groups for which these flavors were presented isolated. In Experiment 3 a group of rats was preexposed to a block of SaltX presentations followed by a block of BX presentations (SaltX-BX), and a second group received blocked preexposure to (BX-SaltX). After subsequent sodium depletion, consumption of X was high and similar for the SaltX-BX and for the BX-SaltX groups. These results indicate that the within-compound association established in the first block of a blocked preexposure is not extinguished when the preexposure phase is concluded.

L-DOPA treatment selectively restores spine density in dopamine receptor D2-expressing projection neurons in dyskinetic mice.

BACKGROUND: L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia is an incapacitating complication of L-DOPA therapy that affects most patients with Parkinson's disease. Previous work indicating that molecular sensitization to dopamine receptor D1 (D1R) stimulation is involved in dyskinesias prompted us to perform electrophysiological recordings of striatal projection "medium spiny neurons" (MSN). Moreover, because enhanced D1R signaling in drug abuse induces changes in spine density in striatum, we investigated whether the dyskinesia is related to morphological changes in MSNs. METHODS: Wild-type and bacterial artificial chromosome transgenic mice (D1R-tomato and D2R-green fluorescent protein) mice were lesioned with 6-hydroxydopamine and subsequently treated with L-DOPA to induce dyskinesia. Functional, molecular, and structural changes were assessed in corticostriatal slices. Individual MSNs injected with Lucifer-Yellow were detected by immunohistochemistry for three-dimensional reconstructions with Neurolucida software. Intracellular current-clamp recordings with high-resistance micropipettes were used to characterize electrophysiological parameters. RESULTS: Both D1R-MSNs and D2R-MSNs showed diminished spine density in totally denervated striatal regions in parkinsonian mice. Chronic L-DOPA treatment, which induced dyskinesia and aberrant FosB expression, restored spine density in D2R-MSNs but not in D1R-MSNs. In basal conditions, MSNs are more excitable in parkinsonian than in sham mice, and excitability decreases toward normal values after L-DOPA treatment. Despite this normalization of basal excitability, in dyskinetic mice, the selective D1R agonist SKF38393 increased the number of evoked action potentials in MSNs, compared with sham animals. CONCLUSIONS: Chronic L-DOPA induces abnormal spine re-growth exclusively in D2R-MSNs and robust supersensitization to D1R-activated excitability in denervated striatal MSNs. These changes might constitute the anatomical and electrophysiological substrates of dyskinesia.

Order effects after blocked preexposure to two compound flavors.

In the first three experiments two groups of rats received prolonged blocked preexposure to AX-BX or to BX-AX. Experiment 1 showed that conditioning of AX after preexposure resulted in less generalization to BX in the AX-BX group than in the BX-AX group. Experiments 2 and 3 constituted, respectively, retardation and summation tests of the inhibitory properties acquired by B after preexposure and conditioning of A. Excitatory conditioning of B was retarded in the AX-BX group (Experiment 2) and only in this group B was able to alleviate the aversion conditioned to a new stimulus (Experiment 3). These results are explained as a consequence of the formation, in the AX-BX group, of inhibitory associations directed from B to A. A fourth experiment provided evidence that the A↔X association was preserved until the end of the preexposure phase in this group, which is a requisite for the formation of these inhibitory associations.

Effects of neonatal handling on playfulness by means of reversal of the desire to play in rats (Rattus norvegicus).

In the present study the authors sought to establish whether the range of effects of neonatal handling stimulation (H), that is, brief daily periods of infant isolation, could be extended to the domain of social motivation. With this aim, the authors studied the innate motivation to engage in rough-and-tumble play (R&T) in adolescent rats (Rattus norvegicus) by means of a reversal design, in which half of the rats were first housed in isolation (Days 1-3), and then in company (Days 4-6), while the other half followed the reverse sequence of housing conditions. Results showed in a clear-cut manner that H fuelled playfulness, as measured by pin and dorsal contact episodes, with (relative) independence of trait-based differences in fearful behavior between handled and nonhandled rats. Given that the different levels of the rat's social brain are apparently sensitive to tactile stimulation in infancy, the authors propose that the vibrant R&T reported here could reflect an enduring alteration of genetically based, motivational systems underlying playfulness and, perhaps, positive social emotions like joy.