Interactions between Prefrontal Cholinergic and Glutamatergic Signaling Support Attentional Function.

Attentional processes and capacities are central to cognitive performance. Cortically projecting cholinergic neurons of the basal forebrain are essential components of the neural systems underlying attentional function; however exactly how the cholinergic system supports attentional performance remains unknown. Our current model suggests that transient (scale of seconds) increases in acetylcholine (ACh) release in the prefrontal cortex foster the detection of predictive cues, and that the generation of such transients is dictated by glutamate released from mediodorsal thalamic afferents and the stimulation of ionotropic glutamate receptors. The studies that informed this model were based on data from anesthetized preparations and animals performing relatively simple instrumental tasks. Two of the primary aims of the work going in to my dissertation were to utilize a novel technique with a high degree of temporal precision to record glutamatergic and cholinergic activity in animals performing a sustained attention task (SAT) to characterize how these two major neurotransmitter systems interact to support attentional performance. The major results from these studies are that in contrast to signal detection per se, transient increases in ACh release mediate performance on signal trials requiring a shift from cue-independent to cue-dependent processing. The pattern of glutamate release in task performing animals suggests that in addition to recruiting cholinergic mechanisms, glutamate plays an additional role in signaling choice. Finally our work revealing the interactions between cholinergic and glutamatergic mechanisms additionally predict and explain the observation that α4β2 nAChR agonists more robustly enhance attentional performance in the distractor version of the SAT than the non-selective nAChR agonist nicotine. The results from these studies suggest the limited beneficial effects of nicotine are due to its stimulation of long lasting release events that are unlikely to support specific cognitive operations. Collectively, the work included here has 1) redefined the role of cholinergic transient in attention 2) begun to explore the complex interplay between glutamatergic and cholinergic signaling in cognitive performance 3) demonstrated that by building upon our knowledge of the functions of and interactions between these two systems we can predict the pro-attentional efficacy of putative cognition enhancers.Ph.D.PsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/91399/1/wmhowe_1.pd

Differential Dynamics of Activity Changes in Dorsolateral and Dorsomedial Striatal Loops during Learning

The basal ganglia are implicated in a remarkable range of functions influencing emotion and cognition as well as motor behavior. Current models of basal ganglia function hypothesize that parallel limbic, associative, and motor cortico-basal ganglia loops contribute to this diverse set of functions, but little is yet known about how these loops operate and how their activities evolve during learning. To address these issues, we recorded simultaneously in sensorimotor and associative regions of the striatum as rats learned different versions of a conditional T-maze task. We found highly contrasting patterns of activity in these regions during task performance and found that these different patterns of structured activity developed concurrently, but with sharply different dynamics. Based on the region-specific dynamics of these patterns across learning, we suggest a working model whereby dorsomedial associative loops can modulate the access of dorsolateral sensorimotor loops to the control of action.National Institutes of Health (U.S.) (MH60379)United States. Office of Naval Research (N000140410208)Stanley H. and Sheila G. Sydney FundEuropean Union (Grant 201716)McGovern Institute for Brain Research at MIT (Fellowship

Deterministic functions of cortical acetylcholine

Traditional descriptions of the basal forebrain cholinergic projection system to the cortex have focused on neuromodulatory influences, that is, mechanisms that modulate cortical information processing but are not necessary for mediating discrete behavioral responses and cognitive operations. This review summarises and conceptualises the evidence in support of more deterministic contributions of cholinergic projections to cortical information processing. Through presynaptic receptors expressed on cholinergic terminals, thalamocortical and corticocortical projections can evoke brief cholinergic release events. These acetylcholine ( AC h) release events occur on a fast, sub‐second to seconds‐long time scale (‘transients’). In rats performing a task requiring the detection of cues as well as the report of non‐cue events cholinergic transients mediate the detection of cues specifically in trials that involve a shift from a state of monitoring for cues to cue‐directed responding. Accordingly, ill‐timed cholinergic transients, generated using optogenetic methods, force false detections in trials without cues. We propose that the evidence is consistent with the hypothesis that cholinergic transients reduce detection uncertainty in such trials. Furthermore, the evidence on the functions of the neuromodulatory component of cholinergic neurotransmission suggests that higher levels of neuromodulation favor staying‐on‐task over alternative action. In other terms, higher cholinergic neuromodulation reduces opportunity costs. Evidence indicating a similar integration of other ascending projection systems, including noradrenergic and serotonergic systems, into cortical circuitry remains sparse, largely because of the limited information about local presynaptic regulation and the limitations of current techniques in measuring fast and transient neurotransmitter release events in these systems. Traditional descriptions of the basal forebrain cholinergic projection system to the cortex focused on neuromodulatory influences, that is, mechanisms that modulate cortical information processing but are not necessary for mediating discrete behavioral responses and cognitive operations. This review summarises and conceptualises the evidence in support of more deterministic contributions of cholinergic projections to cortical information processing.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107385/1/ejn12515.pd

Social Competence Treatment after Traumatic Brain Injury: A Multicenter, Randomized, Controlled Trial of Interactive Group Treatment versus Non-Interactive Treatment

Objective To evaluate the effectiveness of a replicable group treatment program for improving social competence after traumatic brain injury (TBI). Design Multicenter randomized controlled trial comparing two methods of conducting a social competency skills program, an interactive group format versus a classroom lecture. Setting Community and Veteran rehabilitation centers. Participants 179 civilian, military, and veteran adults with TBI and social competence difficulties, at least 6 months post-injury. Experimental Intervention Thirteen weekly group interactive sessions (1.5 hours) with structured and facilitated group interactions to improve social competence. Alternative (Control) Intervention Thirteen traditional classroom sessions using the same curriculum with brief supplemental individual sessions but without structured group interaction. Primary Outcome Measure Profile of Pragmatic Impairment in Communication (PPIC), an objective behavioral rating of social communication impairments following TBI. Secondary Outcomes LaTrobe Communication Questionnaire (LCQ), Goal Attainment Scale (GAS), Satisfaction with Life Scale (SWLS), Post-Traumatic Stress Disorder Checklist – (PCL-C), Brief Symptom Inventory 18 (BSI-18), Scale of Perceived Social Self Efficacy (PSSE). Results Social competence goals (GAS) were achieved and maintained for most participants regardless of treatment method. Significant improvements in the primary outcome (PPIC) and two of the secondary outcomes (LCQ and BSI) were seen immediately post-treatment and at 3 months post-treatment in the AT arm only, however these improvements were not significantly different between the GIST and AT arms. Similar trends were observed for PSSE and PCL-C. Conclusions Social competence skills improved for persons with TBI in both treatment conditions. The group interactive format was not found to be a superior method of treatment delivery in this study

Bostonia: The Boston University Alumni Magazine. Volume 11

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

Preventing farm land price inflation in the midwest

Both a recollection of the disastrous consequences of the inflationary land prices following World War I and recognition o f the possibility of a recurrence have stimulated public interest in information about the current farm real estate situation. This report has been prepared by the North Central Regional Land Tenure Committee for the purpose of presenting an appraisal of the current situation, stimulating discussion of the problems, and outlining the various possible lines of action most often suggested for curbing undesirable developments. The North Central Regional Land Tenure Committee came into existence as the result o f an informal conference sponsored by the Farm Foundation in the spring of 1939 for land economists from the agricultural experiment stations in the Midwest. As an outgrowth of this and subsequent meetings, the director of each station appointed one of his staff to the Regional Land Tenure Committee which also includes representatives from the United States Department of Agriculture. The major function of the committee is to develop an integrated long-time program of research that will lead to the improvement of farm tenure in the region. This report pertaining to land price inflation in the Midwest is the committee’s second formal publication. The first was entitled “Improving Farm Tenure in the Midwest” and was published as Illinois Agricultural Experiment Station Bulletin 502. The present bulletin is based not only on reports collected from sample counties but on observation and study of the situation by at least one representative from each of the participating states. It is impractical to cite specific land market material published by the several cooperating institutions, but such information is available upon request to the participating agencies

Diminished trk A receptor signaling reveals cholinergic‐attentional vulnerability of aging

The cellular mechanisms underlying the exceptional vulnerability of the basal forebrain ( BF ) cholinergic neurons during pathological aging have remained elusive. Here we employed an adeno‐associated viral vector‐based RNA interference ( AAV ‐ RNA i) strategy to suppress the expression of tropomyosin‐related kinase A (trk A ) receptors by cholinergic neurons in the nucleus basalis of M eynert/substantia innominata ( nMB / SI ) of adult and aged rats. Suppression of trk A receptor expression impaired attentional performance selectively in aged rats. Performance correlated with trk A levels in the nMB / SI . trk A knockdown neither affected nMB / SI cholinergic cell counts nor the decrease in cholinergic cell size observed in aged rats. However, trk A suppression augmented an age‐related decrease in the density of cortical cholinergic processes and attenuated the capacity of cholinergic neurons to release acetylcholine ( AC h). The capacity of cortical synapses to release AC h in vivo was also lower in aged/trk A ‐ AAV ‐infused rats than in aged or young controls, and it correlated with their attentional performance. Furthermore, age‐related increases in cortical pro NGF and p75 receptor levels interacted with the vector‐induced loss of trk A receptors to shift NGF signaling toward p75‐mediated suppression of the cholinergic phenotype, thereby attenuating cholinergic function and impairing attentional performance. These effects model the abnormal trophic regulation of cholinergic neurons and cognitive impairments in patients with early A lzheimer's disease. This rat model is useful for identifying the mechanisms rendering aging cholinergic neurons vulnerable as well as for studying the neuropathological mechanisms that are triggered by disrupted trophic signaling. The cellular mechanisms underlying the exceptional vulnerability of the basal forebrain ( BF ) cholinergic neurons during pathological aging have remained elusive. Here we employed an adeno‐associated viral vector‐based RNA interference ( AAV ‐ RNA i) strategy to suppress the expression of trk A receptors by cholinergic neurons in the nucleus basalis of M eynert/substantia innominata (n MB / SI ) of adult and aged rats. This study provides novel evidence that reduced trkA receptors is not sufficient to trigger cholinergic dysfunction. Rather, aging interacts with disrupted trkA signaling to escalate the vulnerability of BF cholinergic neurons and the manifestation of age‐related attentional impairments.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96365/1/ejn12090-sup-0001-SupportingInformation.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/96365/2/ejn12090.pd

On Five-dimensional Superspaces

Recent one-loop calculations of certain supergravity-mediated quantum corrections in supersymmetric brane-world models employ either the component formulation (hep-th/0305184) or the superfield formalism with only half of the bulk supersymmetry manifestly realized (hep-th/0305169 and hep-th/0411216). There are reasons to expect, however, that 5D supergraphs provide a more efficient setup to deal with these and more involved (in particular, higher-loop) calculations. As a first step toward elaborating such supergraph techniques, we develop in this letter a manifestly supersymmetric formulation for 5D globally supersymmetric theories with eight supercharges. Simple rules are given to reduce 5D superspace actions to a hybrid form which keeps manifest only the 4D, N=1 Poincare supersymmetry. (Previously, such hybrid actions were carefully worked out by rewriting the component actions in terms of simple superfields). To demonstrate the power of this formalism for model building applications, two families of off-shell supersymmetric nonlinear sigma-models in five dimensions are presented (including those with cotangent bundles of Kahler manifolds as target spaces). We elaborate, trying to make our presentation maximally clear and self-contained, on the techniques of 5D harmonic and projective superspaces used at some stages in this letter.Comment: 46 pages, 3 figures. V5: version published in JHE

Six-dimensional Supergravity and Projective Superfields

We propose a superspace formulation of N=(1,0) conformal supergravity in six dimensions. The corresponding superspace constraints are invariant under super-Weyl transformations generated by a real scalar parameter. The known variant Weyl super-multiplet is recovered by coupling the geometry to a super-3-form tensor multiplet. Isotwistor variables are introduced and used to define projective superfields. We formulate a locally supersymmetric and super-Weyl invariant action principle in projective superspace. Some families of dynamical supergravity-matter systems are presented.Comment: 39 pages; v3: some modifications in section 2; equations (2.3), (2.14b), (2.16) and (2.17) correcte