Prefrontal Acetylcholine Release Controls Cue Detection on Multiple Timescales

SummaryCholinergic neurons originating from the basal forebrain innervate the entire cortical mantle. Choline-sensitive microelectrodes were used to measure the synaptic release of cortical acetylcholine (ACh) at a subsecond resolution in rats performing a task involving the detection of cues. Cues that were detected, defined behaviorally, evoked transient increases in cholinergic activity (at the scale of seconds) in the medial prefrontal cortex (mPFC), but not in a nonassociational control region (motor cortex). In trials involving missed cues, cholinergic transients were not observed. Cholinergic deafferentation of the mPFC, but not motor cortex, impaired cue detection. Furthermore, decreases and increases in precue cholinergic activity predicted subsequent cue detection or misses, respectively. Finally, cue-evoked cholinergic transients were superimposed over slower (at the timescale of minutes) changes in cholinergic activity. Cortical cholinergic neurotransmission is regulated on multiple timescales to mediate the detection of behaviorally significant cues and to support cognitive performance

Relating constructs of attention and working memory to social withdrawal in Alzheimer's disease and schizophrenia: issues regarding paradigm selection

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Social brain, social dysfunction and social withdrawal

The human social brain is complex. Current knowledge fails to define the neurobiological processes underlying social behaviour involving the (patho-) physiological mechanisms that link system-level phenomena to the multiple hierarchies of brain function. Unfortunately, such a high complexity may also be associated with a high susceptibility to several pathogenic interventions. Consistently, social deficits sometimes represent the first signs of a number of neuropsychiatric disorders including schizophrenia (SCZ), Alzheimer's disease (AD) and major depressive disorder (MDD) which leads to a progressive social dysfunction. In the present review we summarize present knowledge linking neurobiological substrates sustaining social functioning, social dysfunction and social withdrawal in major psychiatric disorders. Interestingly, AD, SCZ, and MDD affect the social brain in similar ways. Thus, social dysfunction and its most evident clinical expression (i.e., social withdrawal) may represent an innovative transdiagnostic domain, with the potential of being an independent entity in terms of biological roots, with the perspective of targeted interventions

Social brain, social dysfunction and social withdrawal

The human social brain is complex. Current knowledge fails to define the neurobiological processes underlying social behaviour involving the (patho-) physiological mechanisms that link system-level phenomena to the multiple hierarchies of brain function. Unfortunately, such a high complexity may also be associated with a high susceptibility to several pathogenic interventions. Consistently, social deficits sometimes represent the first signs of a number of neuropsychiatric disorders including schizophrenia (SCZ), Alzheimer's disease (AD) and major depressive disorder (MDD) which leads to a progressive social dysfunction. In the present review we summarize present knowledge linking neurobiological substrates sustaining social functioning, social dysfunction and social withdrawal in major psychiatric disorders. Interestingly, AD, SCZ, and MDD affect the social brain in similar ways. Thus, social dysfunction and its most evident clinical expression (i.e., social withdrawal) may represent an innovative transdiagnostic domain, with the potential of being an independent entity in terms of biological roots, with the perspective of targeted interventions

Neuropeptide Y et préférences alimentaires chez le rat adulte. Influence des conditions nutritionnelles pré et post-natales

The ailTI of this study was ta cSlablish whether or nol a link ean be made belween nutritional conditions in carly life, food preferences and hYPolhalamic NPY system functioning throughout life. The offspring of dams fcd on unbalanced diet, either a high carbohydrat diet (HC) or a high fat diet (HF), during the gestation and lactation pcriods were compared to rats obtained From dams fed on a well-balanccd diet (C). First, we studied the growth of male offspring from binh until adulthood. The growth of the HC group was similar ta the control group. The HF rats \veighcd less than the other groups at binh, and this difference persisted, until laler in life. At weaning, hypoinsulinemia and hypoglycaemia WOlS established in the HF group in comparison to the C and HC groups. These di fferencesdisappear at adulLhood. After that, we studied the evolution of diet preferences in the three groups Olt different stages of development. The control group did indeed show a preference for the carbohydrate diet.From the 30th day of life. Such a preference was not observed in the two other groups at 30 d~lYS of age, but it appeared later in lire, at 3 months for the HC group and 4 monlhs for the HF group. In addition the nycthemeral rhythm of the consumplion of eaeh macronutriment was modified in the HC and HF groups, in comparison to the C group. Conceming the :NPY system, the principal hypothalamic axis of NPY action fonned by the arcuate and paraventricular nucleus (ARC-PVN) seemed ta be unaltered at wcaning and during adullhaod, with respect ta ilS NPY cancenlratian and mRNA expression. At wcaning, in lllC venlromedian nucleus (cenler of saliety), the NPY was abnormally high in the HC groups. This phenomenon disappeared al adulthood. However, the NPY system remained altered in adulthood, as is shown by the alteralion of the reactivity of the l\rpy system after cenlral NPY injection and the study of hypathalamic release of NPY in vivo. The study of the rcactivity ta l\rpy injection showed that, at adulthoad, the HC rats were Jess sensitive to exogenous NPY than the twa other groups, while the HF group was particularlysensitive. The dynamic study by push-pull technique showed that, after intraperitonea! 2-DeoxyGlucose injection, which staps glucose uli!ization, the HC group reacted by increasing NPl' liberation. On the contrary, the injection of mercaploacetate, which stops fatty acid axidation in mitochondria, did not have any cffcct on this group, but induced increased l\'PY rclcase in the HFgroup.Therefore, the l\rpy system is differently modified in the HC and the HF group, these alteratiol1s are not due ta the same reasons : They Céln be induccd by physiologiea! disordcrs in the HF group, but not in the HC group.To a certain extent, wc can considcr lh~ll an adaptative mechanism occured in carly life as a means at counteract the unbalanced dicl. \\'ell-balanccd diet givcn to the offsprings after weaning facilitated this proccss, particularly in the HC group. By cxtrapolating these resulls in man, \\C can venture ta say that the predisposition to metabolic disordcrs causcd by mothcr's unbalanced diet can be partlyDes rats issus de mères soumises a deux régimes déséquilibrés riches en glucides ou en lipides pendant la gestation et l'allaitement ont été comparés aux descendants de mères ayant ingéré un régime équilibré. Les petits des mères nourries avec un régime hyper lipidique (HF) montrent un déficit pondéral persistant par rapport aux petits issus de mères nourries avec un régime équilibré ou hyper glucidique (hc). Le groupe HF montre une sensibilité plus élevée à l'injection centrale de npy, tandis que celle du groupe hc est plus faible. L'étude dynamique de la libération de npy par la technique de push-pull intracérébrale montre que, suite à l'administration de 2-deoxy-glucose, seul le groupe hc réagit par une augmentation de libération de npy. Par contre, l'injection de mercaptoacetate n'affecte pas ce groupe alors que le groupe HF montre une augmentation de la libération de npy. Ce travail démontre l'importance du régime alimentaire durant la gestation et l'allaitement sur le développement des systèmes centraux régulant le comportement alimentaire

Effects of changing reward on performance of the delayed spatial win-shift radial maze task in pedunculopontine tegmental nucleus lesioned rats

Because it was designed to assess working memory, the delayed spatial win-shift (DSWS) radial maze task has been used to investigate the involvement of corticostriatal structures in executive processing. Excitotoxic lesions of the pedunculopontine tegmental nucleus (PPTg) produce profound deficits in performance of this task that are not accounted for by motor impairment. Thus, PPTg DSWS deficits are hypothesized to support a role for PPTg in complex cognitive processing. However, other studies indicate that the behaviour of PPTg lesioned rats varies depending on level of motivational excitement, assessed by the presence or absence of deprivation, or by manipulations of reward value. Since DSWS performance may also be affected by motivational dysfunction, the present experiment was conducted to examine the effects of post-surgical presentation of a more positive food reward (chocolate drops) on the DSWS retention performance of PPTg lesioned rats. Results confirmed a PPTg lesion deficit: lesioned rats made significantly more errors in both training and test phases, and made errors significantly earlier in their choice sequence in the test phase. Main effects of phase on number of errors indicated that the PPTg test phase deficit was not simply the result of a carry-over impairment from the training phase. PPTg rats receiving chocolate made significantly fewer errors than PPTg rats receiving food pellets. Results suggest that PPTg DSWS deficits are not the result of altered motivation or hedonic appreciation of reward value (or reward change) and therefore support the hypothesis of executive cognitive deficits in PPTg lesioned rats