Cholinergic Mediation of Attention

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74588/1/annals.1417.021.pd

Reporting statistical methods and statistical results in EJN

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73132/1/j.1460-9568.2008.06581.x.pd

NMDA and dopamine interactions in the nucleus accumbens modulate cortical acetylcholine release

The nucleus accumbens (NAC) plays a key role in directing appropriate motor output following the presentation of behaviorally relevant stimuli. As such, we postulate that accumbens efferents also participate in the modulation of neuronal circuits regulating attentional processes directed toward the identification and selection of these stimuli. In this study, N -methyl-d-aspartate (NMDA) and D1 ligands were perfused into the shell region of the NAC of awake rats. Cortical cholinergic transmission, a mediator of attentional processes, was measured via microdialysis probes inserted into the prefrontal cortex (PFC). NMDA perfusions (150 or 250 µm) into NAC resulted in significant increases in acetylcholine (ACh) efflux in PFC (150–200% above baseline levels). Co-administration of the D1 antagonist SCH-23390 (150 µm) markedly attenuated (by approx. 70%) ACh efflux following perfusions of 150 µm NMDA but not following 250 µm NMDA, suggesting that D1 receptor activity contributes to the ability of the lower but not the higher concentration of NMDA to increase cortical ACh release. Collectively, these data reveal a positive modulation of NMDA receptors by D1 receptors in NAC that is expressed trans -synaptically at the level of cortical transmission. This modulation may underlie the coordinated linking of attentional processes and motor output following exposure to salient and behaviorally relevant stimuli.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72309/1/j.1460-9568.2005.04333.x.pd

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

Phasic cholinergic signaling promotes emergence of local gamma rhythms in excitatory–inhibitory networks

Recent experimental results have shown that the detection of cues in behavioral attention tasks relies on transient increases of acetylcholine (ACh) release in frontal cortex and cholinergically driven oscillatory activity in the gamma frequency band (Howe et al. Journal of Neuroscience, 2017, 37, 3215). The cue‐induced gamma rhythmic activity requires stimulation of M1 muscarinic receptors. Using biophysical computational modeling, we show that a network of excitatory (E) and inhibitory (I) neurons that initially displays asynchronous firing can generate transient gamma oscillatory activity in response to simulated brief pulses of ACh. ACh effects are simulated as transient modulation of the conductance of an M‐type K+ current which is blocked by activation of muscarinic receptors and has significant effects on neuronal excitability. The ACh‐induced effects on the M current conductance, gKs, change network dynamics to promote the emergence of network gamma rhythmicity through a Pyramidal‐Interneuronal Network Gamma mechanism. Depending on connectivity strengths between and among E and I cells, gamma activity decays with the simulated gKs transient modulation or is sustained in the network after the gKs transient has completely dissipated. We investigated the sensitivity of the emergent gamma activity to synaptic strengths, external noise and simulated levels of gKs modulation. To address recent experimental findings that cholinergic signaling is likely spatially focused and dynamic, we show that localized gKs modulation can induce transient changes of cellular excitability in local subnetworks, subsequently causing population‐specific gamma oscillations. These results highlight dynamical mechanisms underlying localization of ACh‐driven responses and suggest that spatially localized, cholinergically induced gamma may contribute to selectivity in the processing of competing external stimuli, as occurs in attentional tasks.Recent experiments showed that cholinergic signaling in the prefrontal cortex is fast and spatially localized in the context of attentional behavioral tasks. The cholinergic transients also generated gamma frequency oscillations that contributed to successful attentional performance. Using computational modeling, we show that transient cholinergic modulation of neural excitability induced the emergence of transient synchronous gamma activity from a background of asynchronous firing in excitatory–inhibitory neural networks.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162747/2/ejn14744.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162747/1/ejn14744_am.pd

EJN in the digital age: introducing the ‘EJN blog’

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88053/1/j.1460-9568.2011.07945.x.pd

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

‘Hot’ vs. ‘cold’ behavioural‐cognitive styles: motivational‐dopaminergic vs. cognitive‐cholinergic processing of a Pavlovian cocaine cue in sign‐ and goal‐tracking rats

Discrete Pavlovian reward cues acquire more potent incentive motivational properties (incentive salience) in some animals (sign‐trackers; STs) compared to others (goal‐trackers; GTs). Conversely, GTs appear to be better than STs in processing more complex contextual cues, perhaps reflecting their relatively greater bias for goal‐directed cue processing. Here, we investigated the activity of two major prefrontal neuromodulatory input systems, dopamine (DA) and acetylcholine (ACh), in response to a discrete Pavlovian cue that was previously paired with cocaine administration in STs and GTs. Rats underwent Pavlovian training in which light cue presentations were either paired or unpaired with an intravenous cocaine infusion. Following a 10‐day abstinence period, prefrontal dialysates were collected in STs and GTs during cue presentations in the absence of cocaine. In STs, the cue previously paired with cocaine significantly increased prefrontal DA levels. DA levels remained elevated over baseline across multiple cue presentation blocks, and DA levels and approaches to the cue were significantly correlated. In STs, ACh levels were unaffected by cue presentations. In contrast, in GTs, presentations of the cocaine cue increased prefrontal ACh, but not DA, levels. GTs oriented towards the cue at rates similar to STs, but they did not approach it and elevated ACh levels did not correlate with conditioned orientation. The results indicate a double dissociation between the role of prefrontal DA and ACh in STs and GTs, and suggest that these phenotypes will be useful for studying the role of neuromodulator systems in mediating opponent behavioural‐cognitive styles.We investigated the activity of two major prefrontal neuromodulatory input systems, dopamine (DA) and acetylcholine (ACh), in response to a Pavlovian cue that was previously paired with cocaine administration in STs and GTs. Following an abstinence period and in the absence of cocaine, cue presentations (C1–C4) in STs resulted in increases in extracellular DA, but not ACh, levels (left). In contrast, cue presentations in GTs increased ACh, but not DA, levels (NC, no‐cue).Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141035/1/ejn13741_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141035/2/ejn13741-sup-0001-reviewer_comments.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141035/3/ejn13741.pd

Connaître les plantes utiles pour l’Agriculture Biologique d’après la littérature : Construction et exploration d’une base de connaissances pour la santé végétale et animale

Organic Farming excludes the use of synthetic chemicals to protect plants in the field or during grain storage and questions the use of antibiotics for livestock breeding or aquaculture. One way to limit major constraints of chemicals (pests and diseases) is to use active plants parts or plants-based products, as it has been described in the literature for plant and animal health. Our current work consists in building a knowledge database from existing literature and implementing exploration methods to support the extraction of knowledge by the potential users (smallholders, advisors, extensionists, researchers, producers, etc.). In early May 2018, the knowledge base gathered data from 227 published documents, dated from 1957 to 2017. Ninety-four percent of the 33,400 uses recorded concerned sub-Saharan African countries

Targeting the pedunculopontine nucleus in Parkinson’s disease: Time to go back to the drawing board

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147041/1/mds27540.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147041/2/mds27540_am.pd