Sustained rescue of prefrontal circuit dysfunction by antidepressant-induced spine formation.

The neurobiological mechanisms underlying the induction and remission of depressive episodes over time are not well understood. Through repeated longitudinal imaging of medial prefrontal microcircuits in the living brain, we found that prefrontal spinogenesis plays a critical role in sustaining specific antidepressant behavioral effects and maintaining long-term behavioral remission. Depression-related behavior was associated with targeted, branch-specific elimination of postsynaptic dendritic spines on prefrontal projection neurons. Antidepressant-dose ketamine reversed these effects by selectively rescuing eliminated spines and restoring coordinated activity in multicellular ensembles that predict motivated escape behavior. Prefrontal spinogenesis was required for the long-term maintenance of antidepressant effects on motivated escape behavior but not for their initial induction.

Activation of a novel p70 S6 kinase 1-dependent intracellular cascade in the basolateral nucleus of the amygdala is required for the acquisition of extinction memory.

Repeated presentations of a previously conditioned stimulus lead to a new form of learning known as extinction, which temporarily alters the response to the original stimulus. Previous studies have shown that the consolidation of extinction memory requires de novo protein synthesis. However, the role of specific nodes of translational control in extinction is unknown. Using auditory threat conditioning in mice, we investigated the role of mechanistic target of rapamycin complex 1 (mTORC1) and its effector p70 S6 kinase 1 (S6K1) in the extinction of auditory threat conditioning. We found that rapamycin attenuated the consolidation of extinction memory. In contrast, genetic deletion and pharmacological inhibition of S6K1, a downstream effector of mTORC1, blocked within-session extinction, indicating a role for S6K1 independent of protein synthesis. Indeed, the activation of S6K1 during extinction required extracellular signal-regulated kinase (ERK) activation in the basolateral nucleus of the amygdala (BLA) and was necessary for increased phosphorylation of the GluA1 (Thr840) subunit of the AMPA receptor following extinction training. Mice exposed to brief uncontrollable stress showed impaired within-session extinction as well as a downregulation of ERK and S6K1 signaling in the amygdala. Finally, using fiber photometry we were able to record calcium signals in vivo, and we found that inhibition of S6K1 reduces extinction-induced changes in neuronal activity of the BLA. These results implicate a novel ERK-S6K1-GluA1 signaling cascade critically involved in extinction.

Psychosocial stress reversibly disrupts prefrontal processing and attentional control.

Relatively little is known about the long-term neurobiological sequelae of chronic stress, which predisposes susceptible patients to neuropsychiatric conditions affecting the prefrontal cortex (PFC). Animal models and human neuroimaging experiments provide complementary insights, yet efforts to integrate the two are often complicated by limitations inherent in drawing comparisons between unrelated studies with disparate designs. Translating from a rodent model of chronic stress where we have shown reversible disruption of PFC function, we show that psychosocial stress induces long-lasting but reversible impairments in behavioral and functional magnetic resonance imaging (fMRI) measures of PFC function in humans. Twenty healthy adults, exposed to 1 month of psychosocial stress, confirmed by a validated rating scale, were scanned while performing a PFC-dependent attention-shifting task. One month later, they returned for a second scanning session after a period of reduced stress, and their performance was compared with a twice-scanned, matched group of low-stress controls. Psychosocial stress selectively impaired attentional control and disrupted functional connectivity within a frontoparietal network that mediates attention shifts. These effects were reversible: after one month of reduced stress, the same subjects showed no significant differences from controls. These results highlight the plasticity of PFC networks in healthy human subjects and suggest one mechanism by which disrupted plasticity may contribute to cognitive impairments characteristic of stress-related neuropsychiatric conditions in susceptible individuals.

The role of faculty development in physiotherapy education.

In recent years there has been a considerable change in the skills and qualifications necessary for faculty members in physiotherapy schools. The focus has shifted considerably from a primary emphasis on the clinical ability of all staff, toward the more universal scholastic goals of research, grants, publications, consultancies and teaching skills. From an absolute reliance on medical research, physiotherapy has had to learn how to go about its own research and apply it directly to treatment modalities and clinical programmes. These changes have had a profound and direct effect on the faculty of physiotherapy schools, while the profession as a whole struggles to come to terms with the change. As is the case in other long established professions, physiotherapy is learning to prize scholastic advancement and research as much as clinical excellence.

The role of the physiotherapist in the management of repetitive strain injury.

A review of current literature concerning the aetiology, diagnosis, role and involvement of physiotherapists in the treatment of repetitive strain injury (R.S.I.) is presented as a basis for investigation. To determine the modes of treatment used by physiotherapists in the management of R.S.I. and to analyse their efficacy, a questionnaire was designed. Forty centres were surveyed and the results are presented. Information concerning the most commonly encountered conditions, treatment given, and physiotherapists' opinions on prevention, patient education and further training in RSI management was also sought. An attempt is made to define the role of the physiotherapist in the recognition, treatment and education aspects of over-use injury, and recommendations for further research and physiotherapy involvement are presented.

Scoliosis: a review.

School screening of adolescents reveals a high prevalence of mild rotational deformity. The objective of screening is to prevent serious deformity by regular review of these children, early recognition of progression and provision of spinal bracing for curves greater than 25°. Two per cent of students screened in the age range 11-13 years have curves greater than 10° but only two per thousand screened require active treatment. A programme of exercise combined with bracing until skeletal maturity is reached, obviates the need for major surgery. Indications for follow-up and treatment are reviewed, and some current concepts of the aetiology of idiopathic scoliosis are examined with particular emphasis on the relationship between scoliosis and growth.

An evaluation of school screening for scoliosis in Western australia.

This paper summarizes the results of research into the scoliosis screening programme undertaken in Western Australian schools over a three-year period from October 1976 to October 1979. It represents the follow-up operating in the spinal deformities clinics chiefly at the Princess Margaret Hospital for Children and also at the Royal Perth (Rehabilitation) Hospital giving details of numbers seen, sex and age relationship, necessity for review visits and active treatment required. The various treatments are outlined briefly. The optimum school levels at which screening should be carried out have emerged and the programme has been altered accordingly as from the beginning of 1980. This paper concludes that school screening for scoliosis is a worthwhile exercise in preventive medicine.