Influence of Classroom Acoustics on Noise Disturbance and Well-Being for First Graders.

Several studies have shown so far that poor acoustics inside classrooms negatively affects the teaching and learning processes, especially at the lowest grades of education. However, the extent to which noise exposure or excessive reverberation affect well-being of children at school in their early childhood is still unanswered, as well as their awareness of noise disturbance. This work is a pilot study to investigate to which extent classroom acoustics affects the perceived well-being and noise disturbance in first graders. About 330 pupils aged from 6 to 7 years participated in the study. They belonged to 20 classes of 10 primary schools located in Torino (Italy), where room acoustic measurements were performed and where noise level was monitored during classes. The school buildings and the classrooms were balanced between socioeconomic status and acoustic conditions. Trained experimenters administered questionnaires in each class, where pupils answered all together during the last month of the school year (May). Questions included the happiness scale, subscales assessing self-esteem, emotional health, relationship at home and with friends, enjoyment of school, intensity and noise disturbance due to different sound sources, and quality of voice. The findings of the study suggest that long reverberation times, which are associated with poor classroom acoustics as they generate higher noise levels and degraded speech intelligibility, bring pupils to a reduced perception of having fun and being happy with themselves. Furthermore, bad classroom acoustics is also related to an increased perception of noise intensity and disturbance, particularly in the case of traffic noise and noise from adjacent school environments. Finally, happy pupils reported a higher perception of noise disturbance under bad classroom acoustic conditions, whereas unhappy pupils only reported complaints in bad classroom acoustics with respect to the perception of pleasances with himself or herself and of fitting in at school. Being a mother tongue speaker is a characteristic of children that brings more chances of attending classes in good acoustics, of being less disturbed, and of having more well-being, and richer districts presented better acoustic conditions, in turn resulting in richer districts also revealing a greater perception of well-being.

Influence of classroom acoustics on the reading speed: A case study on Italian second-graders.

The need of tuning into speech in noisy and reverberant classrooms is a challenge for good speech communication and literacy development at school. Reading development can be compromised if children are exposed to inadequate acoustics, especially those with poor neural processing in speech discrimination. This work reports preliminary results on the influence of classroom acoustics on the reading speed of 94 Italian second-graders. Speech clarity (C50) was found to be significantly correlated with all the investigated reading tasks, while no significant correlations were found with reverberation time.

Region- and Layer-Specific Activation of the Higher Order Auditory Cortex Te2 after Remote Retrieval of Fear or Appetitive Memories.

The auditory cortex is involved in encoding sounds which have acquired an emotional-motivational charge. However, the neural circuitry engaged by emotional memory processes in the auditory cortex is poorly understood. In this study, we investigated the layers and regions that are recruited in the higher order auditory cortex Te2 by a tone previously paired to either fear or appetitive stimuli in rats. By tracking the protein coded by the immediate early gene zif268, we found that fear memory retrieval engages layers II-III in most regions of Te2. These results were neither due to an enhanced fear state nor to fear-evoked motor responses, as they were absent in animals retrieving an olfactory fear memory. These layers were also activated by appetitive auditory memory retrieval. Strikingly, layer IV was recruited by fear, but not appetitive memories, whereas layer V activity was related to the behavioral responses displayed to the CS. In addition to revealing the layers and regions that are recruited in the Te2 by either fear or appetitive remote memories, our study also shows that the neural circuitry within the Te2 that processes and stores emotional memories varies on the basis of the affective motivational charge of tones.

Quality of life, clinical outcome, personality and coping in chronic hemodialysis patients.

RATIONAL: Our aim was to investigate the quality of life (QoL) in 103 patients undergoing chronic hemodialysis (HD) in an integrated assessment of clinical, personological, and adaptation parameters, also in a non-urban context. OBJECTIVES: We collected data from all chronic HD patients attending four HD units. Clinical status was assessed by Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines and by Age-adjusted Charlson Comorbidity Index (ACCI). Patients completed the following questionnaires: Kidney Disease Quality of Life Short Form (KDQOL-SF), Pittsburgh Sleep Quality Index (PSQI). Personality profile and coping style were assessed by Temperament and Character Inventory (TCI) revised and Coping Inventory for Stressful Situation (CISS). Data were analyzed by conventional descriptive statistics. Multiple forward stepwise linear regression analyses were performed. MAIN FINDINGS: Variables significantly associated with physical and mental components of KDQOL-SF were: intact parathyroid hormone (iPTH) (p = .004; p = .0015), typology of cohabitant (family member or not) (p = .022; p = .007), years of dialysis (p = .022; p = .048). Variables associated with mental component of KDQOL-SF were: PSQI (p = .000), task-coping (p = .000), avoidance-coping (p = .003), work status (p = .021). Principle conclusions: Our results suggest the importance of an integrated and multidirectional management of patients chronically undergoing HD and living in a non-urban context.

Higher-Order Sensory Cortex Drives Basolateral Amygdala Activity during the Recall of Remote, but Not Recently Learned Fearful Memories.

Negative experiences are quickly learned and long remembered. Key unresolved issues in the field of emotional memory include identifying the loci and dynamics of memory storage and retrieval. The present study examined neural activity in the higher-order auditory cortex Te2 and basolateral amygdala (BLA) and their crosstalk during the recall of recent and remote fear memories. To this end, we obtained local field potentials and multiunit activity recordings in Te2 and BLA of rats that underwent recall at 24 h and 30 d after the association of an acoustic conditioned (CS, tone) and an aversive unconditioned stimulus (US, electric shock). Here we show that, during the recall of remote auditory threat memories in rats, the activity of the Te2 and BLA is highly synchronized in the theta frequency range. This functional connectivity stems from memory consolidation processes because it is present during remote, but not recent, memory retrieval. Moreover, the observed increase in synchrony is cue and region specific. A preponderant Te2-to-BLA directionality characterizes this dialogue, and the percentage of time Te2 theta leads the BLA during remote memory recall correlates with a faster latency to freeze to the auditory conditioned stimulus. The blockade of this information transfer via Te2 inhibition with muscimol prevents any retrieval-evoked neuronal activity in the BLA and animals are unable to retrieve remote memories. We conclude that memories stored in higher-order sensory cortices drive BLA activity when distinguishing between learned threatening and neutral stimuli. SIGNIFICANCE STATEMENT: How and where in the brain do we store the affective/motivational significance of sensory stimuli acquired through life experiences? Scientists have long investigated how "limbic" structures, such as the amygdala, process affective stimuli. Here we show that retrieval of well-established threat memories requires the functional interplay between higher-order components of the auditory cortex and the amygdala via synchrony in the theta range. This functional connectivity is a result of memory consolidation processes and is characterized by a predominant cortical to amygdala direction of information transfer. This connectivity is predictive of the animals' ability to recognize auditory stimuli as aversive. In the absence of this necessary cortical activity, the amygdala is unable to distinguish between frightening and neutral stimuli.

The higher order auditory cortex is involved in the assignment of affective value to sensory stimuli.

The sensory cortex participates in emotional memory but its role is poorly understood. Here we show that inactivation of the higher order auditory cortex Te2 in rats during early memory consolidation impairs remote first- and second-order fear memories but not the association between two neutral cues. Furthermore, Te2 inactivation prevents changes in the valence of such information. Following the presentation of two auditory cues previously paired with either pleasant or painful stimuli, a large percentage of cells responds to both experiences but also a small fraction of neurons responds exclusively to one of them. The latter type of neurons signals the valence rather than the salience or the motor responses associated with the stimuli, and reflects selective associative processes. Pharmacogenetic silencing of memory-activated neurons causes amnesia. Thus, Te2 represents a crucial node for the assignment of the affective value to sensory stimuli and for the storage of such information.

Basolateral amygdala inactivation impairs learning-induced long-term potentiation in the cerebellar cortex.

Learning to fear dangerous situations requires the participation of basolateral amygdala (BLA). In the present study, we provide evidence that BLA is necessary for the synaptic strengthening occurring during memory formation in the cerebellum in rats. In the cerebellar vermis the parallel fibers (PF) to Purkinje cell (PC) synapse is potentiated one day following fear learning. Pretraining BLA inactivation impaired such a learning-induced long-term potentiation (LTP). Similarly, cerebellar LTP is affected when BLA is blocked shortly, but not 6 h, after training. The latter result shows that the effects of BLA inactivation on cerebellar plasticity, when present, are specifically related to memory processes and not due to an interference with sensory or motor functions. These data indicate that fear memory induces cerebellar LTP provided that a heterosynaptic input coming from BLA sets the proper local conditions. Therefore, in the cerebellum, learning-induced plasticity is a heterosynaptic phenomenon that requires inputs from other regions. Studies employing the electrically-induced LTP in order to clarify the cellular mechanisms of memory should therefore take into account the inputs arriving from other brain sites, considering them as integrative units. Based on previous and the present findings, we proposed that BLA enables learning-related plasticity to be formed in the cerebellum in order to respond appropriately to new stimuli or situations.

Role of secondary sensory cortices in emotional memory storage and retrieval in rats.

Visual, acoustic, and olfactory stimuli associated with a highly charged emotional situation take on the affective qualities of that situation. Where the emotional meaning of a given sensory experience is stored is a matter of debate. We found that excitotoxic lesions of auditory, visual, or olfactory secondary sensory cortices impaired remote, but not recent, fear memories in rats. Amnesia was modality-specific and not due to an interference with sensory or emotional processes. In these sites, memory persistence was dependent on ongoing protein kinase Mzeta activity and was associated with an increased activity of layers II-IV, thus suggesting a synaptic strengthening of corticocortical connections. Lesions of the same areas left intact the memory of sensory stimuli not associated with any emotional charge. We propose that secondary sensory cortices support memory storage and retrieval of sensory stimuli that have acquired a behavioral salience with the experience.

Mouse brain expression patterns of Spg7, Afg3l1, and Afg3l2 transcripts, encoding for the mitochondrial m-AAA protease.

BACKGROUND: The m-AAA (ATPases Associated with a variety of cellular Activities) is an evolutionary conserved metalloprotease complex located in the internal mitochondrial membrane. In the mouse, it is a hetero-oligomer variably formed by the Spg7, Afg3l1, and Afg3l2 encoded proteins, or a homo-oligomer formed by either Afg3l1 or Afg3l2. In humans, AFG3L2 and SPG7 genes are conserved, whereas AFG3L1 became a pseudogene. Both AFG3L2 and SPG7 are involved in a neurodegenerative disease, namely the autosomal dominant spinocerebellar ataxia SCA28 and a recessive form of spastic paraplegia, respectively. RESULTS: Using quantitative RT-PCR, we measured the expression levels of Spg7, Afg3l1, and Afg3l2 in the mouse brain. In all regions Afg3l2 is the most abundant transcript, followed by Spg7, and Afg3l1, with a ratio of approximately 5:3:1 in whole-brain mRNA. Using in-situ hybridization, we showed that Spg7, Afg3l1 and Afg3l2 have a similar cellular pattern of expression, with high levels in mitral cells, Purkinje cells, deep cerebellar nuclei cells, neocortical and hippocampal pyramidal neurons, and brainstem motor neurons. However, in some neuronal types, differences in the level of expression of these genes were present, suggesting distinct degrees of contribution of their proteins. CONCLUSIONS: Neurons involved in SCA28 and hereditary spastic paraplegia display high levels of expression, but similar or even higher expression is also present in other types of neurons, not involved in these diseases, suggesting that the selective cell sensitivity should be attributed to other, still unknown, mechanisms.

Mutations in the mitochondrial protease gene AFG3L2 cause dominant hereditary ataxia SCA28.

Autosomal dominant spinocerebellar ataxias (SCAs) are genetically heterogeneous neurological disorders characterized by cerebellar dysfunction mostly due to Purkinje cell degeneration. Here we show that AFG3L2 mutations cause SCA type 28. Along with paraplegin, which causes recessive spastic paraplegia, AFG3L2 is a component of the conserved m-AAA metalloprotease complex involved in the maintenance of the mitochondrial proteome. We identified heterozygous missense mutations in five unrelated SCA families and found that AFG3L2 is highly and selectively expressed in human cerebellar Purkinje cells. m-AAA-deficient yeast cells expressing human mutated AFG3L2 homocomplex show respiratory deficiency, proteolytic impairment and deficiency of respiratory chain complex IV. Structure homology modeling indicates that the mutations may affect AFG3L2 substrate handling. This work identifies AFG3L2 as a novel cause of dominant neurodegenerative disease and indicates a previously unknown role for this component of the mitochondrial protein quality control machinery in protecting the human cerebellum against neurodegeneration.

Reversible inactivation of amygdala and cerebellum but not perirhinal cortex impairs reactivated fear memories.

The cerebellum, amygdala and perirhinal cortex are involved in fear learning but the different roles that these three structures play in aversive learning are not well defined. Here we show that in adult rats amygdala or cerebellar vermis blockade causes amnesia when performed immediately, but not 1 h, after the recall of fear memories. Thus, the cerebellum, as well as the amygdala, influences long-term fear memories. These effects are long lasting, as they do not recover over time, even after a reminder shock administration. However, all of the subjects were able to form new fear memories in the absence of inactivation. By increasing the strength of conditioning, we observed that stronger fear memories are affected by the combined but not independent amygdala and cerebellar blockade. These results demonstrate that the cerebellum supports the memory processes even in the absence of a crucial site for emotions like the amygdala. Furthermore, they suggest that the amygdala is only one of the neural sites underlying long-term fear memories. Finally, the inactivation of the perirhinal cortex never alters retrieved fear traces, showing important differences between the amygdala, cerebellum and perirhinal cortex in emotional memories.

Properties and expression of Kv3 channels in cerebellar Purkinje cells.

In cerebellar Purkinje cells, Kv3 potassium channels are indispensable for firing at high frequencies. In Purkinje cells from young mice (P4-P7), Kv3 currents, recorded in whole-cell in slices, activated at -30 mV, with rapid activation and deactivation kinetics, and they were partially blocked by blood depressing substance-I (BDS-I, 1 microM). At positive potentials, Kv3 currents were slowly but completely inactivating, while the recovery from inactivation was about eightfold slower, suggesting that a previous firing activity or a small change of the resting potential could in principle accumulate inactivated Kv3 channels, thereby finely tuning Kv3 current availability for subsequent action potentials. Single-cell RT-PCR analysis showed the expression by all Purkinje cells (n=10 for each subunit) of Kv3.1, Kv3.3 and Kv3.4 mRNA, while Kv3.2 was not expressed. These results add to the framework for interpreting the physiological function and the molecular determinants of Kv3 currents in cerebellar Purkinje cells.

Resurgent current and voltage sensor trapping enhanced activation by a beta-scorpion toxin solely in Nav1.6 channel. Significance in mice Purkinje neurons.

Resurgent currents are functionally crucial in sustaining the high frequency firing of cerebellar Purkinje neurons expressing Na(v)1.6 channels. Beta-scorpion toxins, such as CssIV, induce a left shift in the voltage-dependent activation of Na(v)1.2 channels by "trapping" the IIS4 voltage sensor segment. We found that the dangerous Cn2 beta-scorpion peptide induces both the left shift voltage-dependent activation and a transient resurgent current only in human Na(v)1.6 channels (among 1.1-1.7), whereas CssIV did not induce the resurgent current. Cn2 also produced both actions in mouse Purkinje cells. These findings suggest that only distinct beta-toxins produce resurgent currents. We suggest that the novel and unique selectivity of Cn2 could make it a model drug to replace deep brain stimulation of the subthalamic nucleus in patients with Parkinson disease.

Functional roles of an ERG current isolated in cerebellar Purkinje neurons.

Transcripts encoding ERG potassium channels are expressed by most neurons of the CNS. By patch-clamp whole cell recording from Purkinje neurons in slices of young (5-9 days old) mouse cerebellum we have been able to isolate a tail current [IK(ERG)] with the same characteristics as previously described for ERG channels. In zero external Ca2+ and high K+ (40 mM) the V1/2 of activation was -50.7 mV, the V1/2 of inactivation was -70.6 mV, and the deactivation rate was double exponential and voltage dependent. IK(ERG) was 93.0% blocked by WAY-123,398 (1 microM) and 78.2% by haloperidol (2 microM). The role of IK(ERG) on evoked firing was studied in adult mice, where WAY-123,398 application decreased the first spike latency, increased the firing frequency, and suppressed the frequency adaptation. However, the shape of individual action potentials was not affected. Stimulation of presynaptic climbing fibers evoked the Purkinje neuron "complex spike," composed of an initial spike and several spikelets. IK(ERG) block caused an increase of the number of spikelets of the "complex spike." These data show, for the first time, an IK(ERG) in a neuron of the CNS, the cerebellar Purkinje neuron, and indicate that such a current is involved in the control of membrane excitability, firing frequency adaptation, and in determining the effects of the climbing fiber synapse.

A-type potassium currents active at subthreshold potentials in mouse cerebellar Purkinje cells.

Voltage-dependent and calcium-independent K+ currents were whole-cell recorded from cerebellar Purkinje cells in slices. Tetraethylammonium (TEA, 4 mM) application isolated an A-type K+ current (I(K(A))) with a peak amplitude, at +20 mV, of about one third of the total voltage-dependent and calcium-independent K+ current. The I(K(A)) activated at about -60 mV, had a V(0.5) of activation of -24.9 mV and a V(0.5) of inactivation of -69.2 mV. The deactivation time constant at -70 mV was 3.4 +/- 0.4 ms, while the activation time constant at +20 mV was 0.9 +/- 0.2 ms. The inactivation kinetics was weakly voltage dependent, with two time constants; those at +20 mV were 19.3 +/- 3.1 and 97.6 +/- 9.8 ms. The recovery from inactivation had two time constants of 60.8 ms (78.4 %) and 962.3 ms (21.6 %). The I(K(A)) was blocked by 4-aminopyridine with an IC50 of 67.6 microM. Agitoxin-2 (2 nM) blocked 17.4 +/- 2.1 % of the I(K(A)). Flecainide completely blocked the I(K(A)) with a biphasic effect with IC50 values of 4.4 and 183.2 microM. In current-clamp recordings the duration of evoked action potentials was affected neither by agitoxin-2 (2 nM) nor by flecainide (3 microM), but action potentials that were already broadened by TEA were further prolonged by 4-aminopyridine (100 microM). The amplitude of the hyperpolarisation at the end of depolarising steps was reduced by all these blockers.