Quantification of the total neuronal structure of the fear conditioning circuit of the lateral amygdala of the rat

During Pavlovian auditory fear conditioning a previously neutral auditory stimulus (CS) gains emotional significance through pairing with a noxious unconditioned stimulus (US). These associations are believed to be formed by way of plasticity at auditory input synapses on principal neurons in the lateral nucleus of the amygdala (LA). In order to begin to understand how fear memories are stored and processed by synaptic changes in the LA, we have quantified both the entire neural number and the sub-cellular structure of LA principal neurons.We first used stereological cell counting methods on Gimsa or GABA immunostained rat brain. We identified 60,322+/-1408 neurons in the LA unilaterally (n=7). Of these 16,917+/-471 were GABA positive. The intercalated nuclei were excluded from the counts and thus GABA cells are believed to represent GABAergic interneurons. The sub-nuclei of the LA were also independently counted. We then quantified the morphometric properties of in vitro electrophysiologically identified principal neurons of the LA, corrected for shrinkage in xyz planes. The total dendritic length was 9.97+/-2.57mm, with 21+/-4 nodes (n=6). Dendritic spine density was 0.19+/-0.03 spines/um (n=6). Intra-LA axon collaterals had a bouton density of 0.1+/-0.02 boutons/um (n=5). These data begin to reveal the finite cellular and sub-cellular processing capacity of the lateral amygdala, and should facilitate efforts to understand mechanisms of plasticity in LA.

Variable phenotype in 16p duplication within a family

Background More individuals are now being identified with very rare genetic syndromes. We present a family with an inherited duplication of 16p11.2 to 16q12.1 in ring formation. Three of the four children, (aged 15 months to 10 years), mother, uncle, and grandmother are affected. Our aim was to provide preliminary evidence of possible phenotypic patterns of learning and behaviour associated with this chromosome anomaly. Method Psychometric assessments were undertaken with all four children. The mother and uncle also agreed to participate in the study. Measures of development (Bayley or Mullen), intellectual ability (WISC-IV or WAIS-III), academic achievement (WIAT-II), adaptive behaviour (Vinelands), and other relevant aspects of functioning (e.g., Children’s Memory Scale) were administered. Results. The first-born child is the only one who is unaffected. Her intellectual ability was assessed as being within the superior range. The second child experienced early difficulties with speech and motor skills. Although his intelligence is average, he has learning difficulties and significant auditory memory problems. The third child’s speech and motor milestones were markedly delayed. He has a complex medical history that includes a vitamin B12 deficiency. On the Mullen Scales at age 4 his scores ranged from average to very low. The development of the youngest child (aged 15 months), who also had a B12 deficiency but was treated early, was assessed as being within typical limits. Conclusions There is considerable developmental variability among the three children with this inherited 16p duplication. We discuss the intriguing similarities and differences, considering common features that may reflect phenotypic patterns and speculating about possible explanations for the variable presentations.

GABAergic inhibition in the fear conditioning circuit of the lateral amygdala is potentiated by dopamine D1 agonists

Auditory fear conditioning is dependent on auditory signaling from the medial geniculate (MGm) and the auditory cortex (TE3) to principal neurons of the lateral amygdala (LA). Local circuit GABAergic interneurons are known to inhibit LA principal neurons via fast and slow IPSP's. Stimulation of MGm and TE3 produces excitatory post-synaptic potentials in both LA principal and interneurons, followed by inhibitory post-synaptic potentials. Manipulations of D1 receptors in the lateral and basal amygdala modulate the retrieval of learned association between an auditory CS and foot shock. Here we examined the effects of D1 agonists on GABAergic IPSP's evoked by stimulation of MGm and TE3 afferents in vitro. Whole cell patch recordings were made from principal neurons of the LA, at room temperature, in coronal brain slices using standard methods. Stimulating electrodes were placed on the fiber tracts medial to the LA and at the external capsule/layer VI border dorsal to the LA to activate (0.1-0.2mA) MGm and TE3 afferents respectively. Neurons were held at -55.0 mV by positive current injection to measure the amplitude of the fast IPSP. Changes in input resistance and membrane potential were measured in the absence of current injection. Stimulation of MGm or TE3 afferents produced EPSP's in the majority of principal neurons and in some an EPSP/IPSP sequence. Stimulation of MGm afferents produced IPSP's with amplitudes of -2.30 ± 0.53 mV and stimulation of TE3 afferents produced IPSP's with amplitudes of -1.98 ± 1.26 mV. Bath application of 20μM SKF38393 increased IPSP amplitudes to -5.94 ± 1.62 mV (MGm, n=3) and-5.46 ± 0.31 mV (TE3, n=3). Maximal effect occurred <10mins. A small increase in resting membrane potential and decrease in input resistance were observed. These data suggest that DA modulates both the auditory thalamic and auditory cortical inputs to the LA fear conditioning circuit via local GABAergic circuits. Supported by NIMH Grants 00956, 46516, and 58911.

Early maternal deprivation reduces prepulse inhibition and impairs spatial learning ability in adulthood: No further effect of post-pubertal chronic corticosterone treatment

Prolonged maternal deprivation leads to long-term alterations in hypothalamic–pituitary–adrenal (HPA) axis activity, disturbances of auditory information processing and neurochemical changes in the adult brain, some of which are similar to that observed in schizophrenia. Here we report the adult behavioural effects of maternal deprivation (12 h on postnatal days 9 and 11) in Wistar rats on paradigms of auditory information processing (prepulse inhibition), sensitivity to dopamimetics (amphetamine-induced hyper-locomotion) and cognition (T-maze delayed alternation and Morris water-maze). In addition, we examined the long-lasting effect of chronic 21-day corticosterone treatment during the post-pubertal period (i.e., postnatal days 56–76) on each of these behavioural paradigms in maternally deprived and control rats. Behavioural testing commenced 2 weeks after the termination of corticosterone treatment. Maternal deprivation led to a significant reduction in PPI and impaired spatial learning ability in adulthood, but did not affect the behavioural response to amphetamine. Post-pubertal chronic corticosterone treatment did not have any major long-lasting effects on any of the behavioural measures in either maternally deprived or control rats. Our findings further support maternal deprivation as an animal model of specific aspects of schizophrenia.

Identifying mentors’ observations for providing feedback

Mentors’ feedback can assist preservice teachers’ development; yet feedback tends to be variable from one mentor to the next. What do mentors observe for providing feedback? In this study, 24 mentors observed a final-year preservice teacher through a professionally video-recorded lesson and provided written notes for feedback. They observed the lesson for a second time and focused their feedback on the preservice teacher’s questioning only. Findings showed that the mentors’ written feedback varied considerably when open-ended observations occurred. However, there were fewer items when they focused on one teaching practice (i.e., questioning), which also provided a deeper analysis of this specific practice. Research is required around the dimensions of observations (i.e., visual, auditory, and conceptual), observations of specific practices, and methodological approaches for observing and collecting data about a preservice teacher’s practice.

Let’s talk about lex: Narrative analysis as both research method and teaching technique in law

Law is narration: it is narrative, narrator and the narrated. As a narrative, the law is constituted by a constellation of texts – from official sources such as statutes, treaties and cases, to private arrangements such as commercial contracts, deeds and parenting plans. All are a collection of stories: cases are narrative contests of facts and rights; statutes are recitations of the substantive and procedural bases for social, economic and political interactions; private agreements are plots for future relationships, whether personal or professional. As a narrator, law speaks in the language of modern liberalism. It describes its world in abstractions rather than in concrete experience, universal principles rather than individual subjectivity. It casts people into ‘parties’ to legal relationships; structures human interactions into ‘issues’ or ‘problems’; and tells individual stories within larger narrative arcs such as ‘the rule of law’ and ‘the interests of justice’. As the narrated, the law is a character in its own story. The scholarship of law, for example, is a type of story-telling with law as its central character. For positivists, still the dominant group in the legal genre, law is a closed system of formal rules with an “immanent rationality” and its own “structure, substantive content, procedure and tradition,” dedicated to finality of judgment. For scholars inspired by the interpretative tradition in the humanities, law is a more ambivalent character, susceptible to influences from outside its realm and masking a hidden ideological agenda under its cloak of universality and neutrality. For social scientists, law is a protagonist on a wider social stage, impacting on society, the economy and the polity is often surprising ways.

Fear memory reactivation after extinction activates plasticity in the lateral amygdala

Little is known about the neuronal changes that occur within the lateral amygdala (LA) following fear extinction. In fear extinction, the repeated presentation of a conditioned stimulus (CS), in the absence of a previously paired aversive unconditioned stimulus (US), reduces fear elicited by the CS. Fear extinction is an active learning process that leads to the formation of a consolidated extinction memory, however it is fragile and prone to spontaneous recovery and renewal under environmental changes such as context. Understanding the neural mechanisms underlying fear extinction is of great clinical relevance, as psychological treatments of several anxiety disorders rely largely on extinction-based procedures and relapse is major clinical problem. This study investigated plasticity in the LA following fear memory reactivation in rats with and without extinction training. Phosphorylated MAPK (p44/42 ERK/MAPK), a protein kinase required in the amygdala for fear learning and its extinction, was used as a marker for neuronal plasticity. Rats (N = 11) underwent a Pavlovian auditory fear conditioning and extinction paradigm, and later received a single conditioned stimulus presentation to reactivate the fear memory. Results showed more pMAPK+ expressing neurons in the LA following extinction-reactivation compared to control rats, with the largest number of pMAPK+ neurons counted in the ventral LA, especially including the ventro-lateral subdivision (LAvl). These findings indicate that LA subdivision specific plasticity occurs to the conditioned fear memory in the LAvl following extinction-reactivation. These findings provide important insight into the organisation of fear memories in the LA, and pave the way for future research in the memory mechanisms of fear extinction and its pathophysiology.

'Free' surfactant in gastric aspirates and bronchoalveolar lavage in children with and without reflux oesophagitis

Aim: Dipalmitoylphosphatidycholine (DPPC) is the characteristic and main constituent of surfactant. Adsorption of surfactant to epithelial surfaces may be important in the masking of receptors. The aims of the study were to (i) compare the quantity of free DPPC in the airways and gastric aspirates of children with gastroesophageal reflux disease (GORD) to those without and (ii) describe the association between free DPPC levels with airway cellular profile and capsaicin cough sensitivity. Methods: Children aged <14 years were defined as 'coughers' if a history of cough in association with their GORD symptoms was elicited before gastric aspirates and nonbronchoscopic bronchoalveolar lavage (BAL) were obtained during elective flexible upper gastrointestinal endoscopy. GORD was defined as histological presence of reflux oesophagitis. Spirometry and capsaicin cough-sensitivity test was carried out in children aged >6 years before the endoscopy. Results: Median age of the 68 children was 9 years (interquartile range (IQR) 7.2). Median DPPC level in BAL of children with cough (72.7 μg/mL) was similar to noncoughers (88.5). There was also no significant difference in DPPC levels in both BAL and gastric aspirates of children classified according to presence of GORD. There was no correlation between DPPC levels and cellular counts or capsaicin cough-sensitivity outcome measures. Conclusion: We conclude that free DPPC levels in the airways and gastric aspirate is not influenced by presence of cough or GORD defined by histological presence of reflux oesophagitis. Whether quantification of adsorbed surfactant differs in these groups remain unknown. Free DPPC is unlikely to have a role in masking of airway receptors. © 2006 Royal Australasian College of Physicians.

Dysbindin (DTNBP1) variants are associated with hallucinations in schizophrenia

BACKGROUND: Dystrobrevin binding protein 1 (DTNBP1) is a schizophrenia susceptibility gene involved with neurotransmission regulation (especially dopamine and glutamate) and neurodevelopment. The gene is known to be associated with cognitive deficit phenotypes within schizophrenia. In our previous studies, DTNBP1 was found associated not only with schizophrenia but with other psychiatric disorders including psychotic depression, post-traumatic stress disorder, nicotine dependence and opiate dependence. These findings suggest that DNTBP1 may be involved in pathways that lead to multiple psychiatric phenotypes. In this study, we explored the association between DTNBP1 SNPs (single nucleotide polymorphisms) and multiple psychiatric phenotypes included in the Diagnostic Interview of Psychosis (DIP). METHODS: Five DTNBP1 SNPs, rs17470454, rs1997679, rs4236167, rs9370822 and rs9370823, were genotyped in 235 schizophrenia subjects screened for various phenotypes in the domains of depression, mania, hallucinations, delusions, subjective thought disorder, behaviour and affect, and speech disorder. SNP-phenotype association was determined with ANOVA under general, dominant/recessive and over-dominance models. RESULTS: Post hoc tests determined that SNP rs1997679 was associated with visual hallucination; SNP rs4236167 was associated with general auditory hallucination as well as specific features including non-verbal, abusive and third-person form auditory hallucinations; and SNP rs9370822 was associated with visual and olfactory hallucinations. SNPs that survived correction for multiple testing were rs4236167 for third-person and abusive form auditory hallucinations; and rs9370822 for olfactory hallucinations. CONCLUSION: These data suggest that DTNBP1 is likely to play a role in development of auditory related, visual and olfactory hallucinations which is consistent with evidence of DTNBP1 activity in the auditory processing regions, in visual processing and in the regulation of glutamate and dopamine activity

Interactions of natural products with β-lactoglobulins, members of the lipocalin family

Natural products constitute an important source of new drugs. The bioavailability of the drugs depends on their absorption, distribution, metabolism and elimination. To achieve good bioavailability, the drug must be soluble in water, stable in the gastrointestinal tract and palatable. Binding proteins may improve the solubility of drug compounds, masking unwanted properties, such as bad taste, bitterness or toxicity, transporting or protecting these compounds during processing and storage. The focus of this thesis was to study the interactions, including ligand binding and the effect of pH and temperature, of bovine and reindeer β-lactoglobulin (βLG) with such compounds as retinoids, phenolic compounds as well as with compounds from plant extracts, and to investigate the transport properties of the βLG-ligand complex. To examine the binding interactions of different ligands to βLG, new methods were developed. The fluorescence binding method for the evaluation of ligand binding to βLG was miniaturized from a quartz cell to a 96-well plate. A method of ultrafiltration sampling combined with high-performance liquid chromatography was developed to assess the binding of compounds from extracts. The interactions of phenolic compounds or retinoids and βLG were investigated using the 96-well plate method. The majority of flavones, flavonols, flavanones and isoflavones and all of the retinoids included were shown to bind to bovine and reindeer βLG. Phenolic compounds, contrary to retinol, were not released at acidic pH. Those results suggest that βLG may have more binding sites, probably also on the surface of βLG. An extract from Camellia sinensis (L.) O. Kunze (black tea), Urtica dioica L. (nettle) and Piper nigrum (black pepper) were used to evaluate whether βLG could bind compounds from plant extracts. Piperine from P. nigrum was found to bind tightly and rutin from U. dioica weakly to βLG. No components from C. sinensis bound to βLG in our experiment. The uptake and membrane permeation of bovine and reindeer βLG, free and bound with retinol, palmitic acid and cholesterol, were investigated using Caco-2 cell monolayers. Both bovine and reindeer βLG were able to cross the Caco-2 cell membrane. Free and βLG-bound retinol and palmitic acid were transported equally, whereas cholesterol could not cross the Caco-2 cell monolayer free or bound to βLG. Our results showed that βLG can bind different natural product compounds, but cannot enhance transport of retinol, palmitic acid or cholesterol through Caco-2 cells. Despite this, βLG, as a water-soluble binding protein, may improve the solubility of natural compounds, possibly protecting them from early degradation and transporting some of them through the stomach. Furthermore, it may decrease their bad or bitter taste during oral administration of drugs or in food preparations. βLG can also enhance or decrease the health benefits of herbal teas and food preparations by binding compounds from extracts.

Spontaanin puheen prosodinen jaksottelu

The common focus of the studies brought together in this work is the prosodic segmentation of spontaneous speech. The theoretically most central aspect is the introduction and further development of the IJ-model of intonational chunking. The study consists of a general introduction and five detailed studies that approach prosodic chunking from different perspectives. The data consist of recordings of face-to-face interaction in several spoken varieties of Finnish and Finland Swedish; the methodology is usage-based and qualitative. The term “speech prosody” refers primarily to the melodic and rhythmic characteristics of speech. Both speaking and understanding speech require the ability to segment the flow of speech into suitably sized prosodic chunks. In order to be usage-based, a study of spontaneous speech consequently needs to be based on material that is segmented into prosodic chunks of various sizes. The segmentation is seen to form a hierarchy of chunking. The prosodic models that have so far been developed and employed in Finland have been based on sentences read aloud, which has made it difficult to apply these models in the analysis of spontaneous speech. The prosodic segmentation of spontaneous speech has not previously been studied in detail in Finland. This research focuses mainly on the following three questions: (1) What are the factors that need to be considered when developing a model of prosodic segmentation of speech, so that the model can be employed regardless of the language or dialect under analysis? (2) What are the characteristics of a prosodic chunk, and what are the similarities in the ways chunks of different languages and varieties manifest themselves that will make it possible to analyze different data according to the same criteria? (3) How does the IJ-model of intonational chunking introduced as a solution to question (1) function in practice in the study of different varieties of Finnish and Finland Swedish? The boundaries of the prosodic chunks were manually marked in the material according to context-specific acoustic and auditory criteria. On the basis of the data analyzed, the IJ-model was further elaborated and implemented, thus allowing comparisons between different language varieties. On the basis of the empirical comparisons, a prosodic typology is presented for the dialects of Swedish in Finland. The general contention is that the principles of the IJ-model can readily be used as a methodological tool for prosodic analysis irrespective of language varieties.

Growth and meaning from negotiating the complex journey of being an Emergency Medical Dispatcher

Emergency Medical Dispatchers (EMDs) are charged with taking the calls of those who ring the national emergency number for urgent medical assistance, for dispatching paramedical crews, and for providing as much assistance as can be offered remotely until paramedics arrive. In a job role which is filled with vicarious trauma, emergency situations, pressure, abuse, grief and loss, EMDs are often challenged in maintaining their mental health. The seemingly senseless death of a teenager who commits suicide, the devastating loss of a baby to Sudden Infant Death Syndrome, lives lost through natural disasters, and multiple vehicle fatalities are only a few of the types of experiences EMDs are faced with in the course of their work. However, amongst the horror are positive stories such as coaching a caller to negotiate the birth of a baby and saving a life in jeopardy from heart failure. EMD’s need to cope with the daily challenges of the role; make sense of their work and create meaning in order to have a fulfilled and sustainable career. Although some people in this work struggle greatly to withstand the impacts of vicarious trauma, there are also stories of personal growth. In this Chapter we use a case study to explore how meaning is made for those who are an auditory witness to a continual flux of trauma for others and how the traumatic experiences EMDs bear witness to can also be a catalyst for posttraumatic growth.

Melun sieto kaupunkielämän välttämättömyytenä : Melu ympäristöongelmana ja sen synnyttämien reaktioiden kulttuurinen käsittely Helsingissä

Tolerance of Noise as a Necessity of Urban Life. Noise pollution as an environmental problem and its cultural perceptions in the city of Helsinki This study looks at the noise pollution problem and the change in the urban soundscape in the city of Helsinki during the period from the 1950s to the present day. The study investigates the formation of noise problems, the politicization of the noise pollution problem, noise-related civic activism, the development of environmental policies on noise, and the expectations that urban dwellers have had concerning their everyday soundscape. Both so-called street noise and the noise caused by, e.g., neighbors are taken into account. The study investigates whether our society contains or has for some time contained cultural and other elements that place noise pollution as an essential or normal state of affairs as part of urban life. It is also discussed whether we are moving towards an artificial soundscape, meaning that the auditory reality, the soundscape, is more and more under human control. The concept of an artificial soundscape was used to crystallize the significance of human actions and the role of modern technology in shaping soundscapes and also to link the changes in the modern soundscape to the economic, political, and social changes connected to the modernization process. It was argued that the critical period defining noise pollution as an environmental problem were the years from the end of the 1960s to the early 1970s. It seems that the massive increase of noise pollution caused by road traffic and the introduction of the utopian traffic plans was the key point that launched the moral protest against the increase of noise pollution, and in general, against the basic structures and mindsets of society, including attitudes towards nature. The study argues that after noise pollution was politicized and institutionalized, the urban soundscape gradually became the target of systematic interventions. However, for various reasons, such as the inconsistency in decision making, our increased capacity to shape the soundscape has not resulted in a healthy or pleasant urban soundscape. In fact the number of people exposed to noise pollution is increasing. It is argued that our society contains cultural and other elements that urge us to see noise as a normal part of urban life. It is also argued that the possibility of experiencing natural, silent soundscapes seems to be the yardstick against which citizens of Helsinki have measured how successful we are in designing the (artificial) soundscape and if the actions of noise control have been effective. This work discusses whose interests it serves when we are asked to accept noise pollution as a normal state of affairs. It is also suggested that the quality of the artificial soundscape ought to be radically politicized, which might give all citizens a better and more equal chance to express their needs and wishes concerning the urban soudscape, and also to decide how it ought to be designed.

Testa din inlärningsstil : En utredning om VAK i undervisning av det andra inhemska språket

This thesis is an investigation of the significance of VAK, i.e. the visual, auditory and kinaesthetic learning styles, for language education. The research part evaluates the predictive validity of a VAK test commonly used in Finnish education. The results of the test were compared, respectively, with the results of a visual, an auditory and a kinaesthetic word test. 62 dyslexic language leaners participated in the tests. There was no statistically significant link between the results of the VAK test and the word tests. On the grounds of a voluntary questionnaire, most of the students did however consider it important that they are taught according to their personal learning style: visual, auditory or kinaesthetic. One of the goals of the study was to investigate the theoretical background of VAK. VAK does not seem to have a consistent theoretical basis, but combines various elements such as NLP pedagogy and Dunn's and Prashnig's learning style models that have previously been sharply criticized by scholars. The study leaves it open whether individual learning styles do exist, and how they could be diagnosed.

Comparison Of If Estimation Methods For Noise Robustness

Non-stationary signal modeling is a well addressed problem in the literature. Many methods have been proposed to model non-stationary signals such as time varying linear prediction and AM-FM modeling, the later being more popular. Estimation techniques to determine the AM-FM components of narrow-band signal, such as Hilbert transform, DESA1, DESA2, auditory processing approach, ZC approach, etc., are prevalent but their robustness to noise is not clearly addressed in the literature. This is critical for most practical applications, such as in communications. We explore the robustness of different AM-FM estimators in the presence of white Gaussian noise. Also, we have proposed three new methods for IF estimation based on non-uniform samples of the signal and multi-resolution analysis. Experimental results show that ZC based methods give better results than the popular methods such as DESA in clean condition as well as noisy condition.