Neuromodulation of Visual Perception

Friday, May 11, 3:30 – 5:30 pm

Organizers: Jutta Billino, Justus-Liebig-University Giessen and Ulrich Ettinger, Rheinische Friedrich-Wilhelms-Universit�t Bonn

Presenters: Anita A. Disney, Salk Institute; Alexander Thiele, Institute of Neuroscience, Newcastle University, Newcastle Upon Tyne, United Kingdom; Behrad Noudoost,Department of Neurobiology, Stanford University School of Medicine; Ariel Rokem, Department of Psychology, Stanford University; Ulrich Ettinger, Rheinische Friedrich-Wilhelms-Universit�t Bonn; Patrick J. Bennett, Department of Psychology, Neuroscience & Behaviour McMaster University

Symposium Description

Over the last decades insights into the neurobiological mechanisms of visual perception have accumulated an impressive knowledge base. However, only recently research has started to uncover how different neurotransmitters affect visual processing. Advances in this research area expand our understanding of the complex regulation of sensory and sensorimotor processes. They moreover shed light on the mechanisms underlying individual differences in visual perception and oculomotor control that have been repeatedly observed, but are still insufficiently understood. The symposium aims to bring together experts in the field that complement each other with regard to different neurotransmitter systems, methods, and implications of their findings. Thus, the audience will be provided with an up-to-date overview of our knowledge on neuromodulation of visual perception. The symposium will start with presentations on physiological data showing the complexity of neuromodulation in early visual cortex. Anita Disney (Salk Institute) has worked together with Mike Hawken (New York University) on cholinergic mechanisms in macaque V1. Their findings show that nicotinergic receptors for acetylcholine are involved in gain modulation. The effects of nicotine application resemble those of attention in the awake monkey. Thus, it has been suggested that attentional effects in V1 activity might be partly mediated by acetylcholine. The presentation by Alexander Thiele and colleagues (Newcastle University) will tie in with the focus on attention. They have studied differential contributions of acetylcholine and glutamate to attentional modulation in V1. They were able to show that both neurotransmitters independently influence firing characteristics of V1 neurons associated with enhanced attention. The work of Behrad Noudoost and Tirin Moore (Stanford University) addresses prefrontal control of visual cortical signals mediated by dopamine. Their findings reveal that dopaminergic manipulation in the frontal eye fields does not only affect saccadic target selection, but also modulates response characteristics of V4 neurons. In the second part of the symposium presentations are supposed to bridge the gap between insights from physiology and behavioral data in humans. Ariel Rokem (Stanford University) and Michael Silver (UC Berkeley) pharmacologically enhanced cholinergic transmission in healthy humans and studied perceptual learning. Results support that acetylcholine increases the effects of perceptual learning which points to its role in regulation of neural plasticity. Ulrich Ettinger (Ludwig-Maximilians-University Munich) will summarize his work on the modulation of oculomotor control by cholinergic and dopaminergic challenges. He has studied effects of pharmacological manipulation as well as of functional genetics on saccadic eye movements. His methods also include imaging and clinical neuropsychology. The symposium will be completed by a presentation of Patrick Bennett and Allison Sekuler (McMaster University) on age-related changes in visual perception and how these can be modeled by altered neurotransmitter activity. The symposium on neuromodulation of visual perception will attract a broad audience because it offers a comprehensive and interdisciplinary overview of recent advances in this innovative research area. Presentations cover fundamental mechanisms of visual processing as well as implications for perception and visuomotor control. Attendees with diverse backgrounds will benefit and will be inspired to apply insights into neuromodulation to their own research field.

Presentations

Modulating visual gain: cholinergic mechanisms in macaque V1

Anita A. Disney, Salk Institute

Michael J. Hawken, Center for Neural Science, New York University

Cholinergic neuromodulation has been suggested to underlie arousal and attention in mammals. Acetylcholine (ACh) is released in cortex by volume transmission and so specificity in its effects must largely be conferred by selective expression of ACh receptors (AChRs). To dissect the local circuit action of ACh, we have used both quantitative anatomy and in vivo physiology and pharmacology during visual stimulation in macaque primary visual cortex (V1). We have shown that nicotinic AChRs are found presynaptically at thalamocortical synapses arriving at spiny neurons in layer 4c of V1 and that nicotine acts in this layer to enhance the gain of visual neurons. Similar evidence for nicotinic enhancement of thalamocortical transmission has been found in the primary cortices of other species and across sensory systems. In separate experiments we have shown that, amongst intrinsic V1 neurons, a higher proportion of GABAergic � in particular parvalbumin-immunoreactive – neurons express muscarinic AChRs than do excitatory neurons. We have also shown that ACh strongly suppresses visual responses outside layer 4c of macaque V1 and that this suppression can be blocked using a GABAa receptor antagonist. Suppression by ACh has been demonstrated in other cortical model systems but is often found to be mediated by reduced glutamate release rather than enhanced release of GABA. Recent anatomical data on AChR expression in the extrastriate visual cortex of the macaque and in V1 of rats, ferrets, and humans, suggest that there may be variation in the targeting of muscarinic mechanisms across neocortical model systems

Differential contribution of cholinergic and glutamatergic receptors to attentional modulation in V1

Alexander Thiele, Institute of Neuroscience, Newcastle University, Newcastle Upon Tyne, United Kingdom, Jose Herreo, Institute of Neuroscience, Newcastle University, Newcastle Upon Tyne, United Kingdom; Alwin Gieselmann, Institute of Neuroscience, Newcastle University, Newcastle Upon Tyne, United Kingdom

In V1, attentional modulation of firing rates is dependent on cholinergic (muscarinic) mechanisms (Herrero et al., 2008). Modelling suggests that appropriate ACh drive enables top-down feedback from higher cortical areas to exert its influence (Deco & Thiele, 2011). The implementation of such feedback at the transmitter/receptor level is poorly understood, but it is generally assumed that feedback relies on ionotropic glutamatergic (iGluR) mechanisms. We investigated this possibility by combining iontophoretic pharmacological analysis with V1 cell recordings while macaques performed a spatial attention task. Blockade or activation of iGluR did not alter attention-induced increases in firing rate, when compared to attend away conditions. However, attention reduced firing rate variance as previously reported in V4 (Mitchell, Sundberg, Reynolds, 2007), and this reduction depended on functioning iGluRs. Attention also reduced spike coherence between simultaneously recorded neurons in V1 as previously demonstrated for V4 (Cohen & Maunsell, 2009; Mitchell et al., 2007). Again, this reduction depended on functional iGluR. Thus overall excitatory drive (probably aided by feedback), increased the signal to noise ratio (reduced firing rate variance) and reduced redundancy of information transmission (noise correlation) in V1. Conversely, attention induced firing rate differences are enabled by the cholinergic system. These studies identify independent contributions of different neurotransmitter systems to attentional modulation in V1.

Dopamine-mediated prefrontal control of visual cortical signals

Behrad Noudoost, Department of Neurobiology, Stanford University School of Medicine, Tirin Moore, Department of Neurobiology, Stanford University School of Medicine & Howard Hughes Medical Institute, Stanford University School of Medicine

Prefrontal cortex (PFC) is believed to play a crucial role in executive control of cognitive functions. Part of this control is thought to be achieved by control of sensory signals in posterior sensory cortices. Dopamine is known to play a role in modulating the strength of signals within the PFC. We tested whether this neurotransmitter is involved in PFC�s top-down control of signals within posterior sensory areas. We recorded responses of neurons in visual cortex (area V4) before and after infusion of the D1 receptor (D1R)-antagonist SCH23390 into the frontal eye field (FEF) in monkeys performing visual fixation and saccadic target selection tasks. Visual stimuli were presented within the shared response fields of simultaneously studied V4 and FEF sites. We found that modulation of D1R-mediated activity within the FEF enhances the strength of visual signals in V4 and increases the monkeys� tendency to choose targets presented within the affected part of visual space. Similar to the D1R manipulation, modulation of D2R-mediated activity within the FEF also increased saccadic target selection. However, it failed to alter visual responses within area V4. The observed effects of D1Rs in mediating the control of visual cortical signals and the selection of visual targets, coupled with its known role in working memory, suggest PFC dopamine as a key player in the control of cognitive functions.

Cholinergic enhancement of perceptual learning in the human visual system

Ariel Rokem, Department of Psychology, Stanford University, Michael A. Silver, Helen Wills Neuroscience Institute and School of Optometry, University of California, Berkeley

Learning from experience underlies our ability to adapt to novel tasks and unfamiliar environments. But how does the visual system know when to adapt and change and when to remain stable? The neurotransmitter acetylcholine (ACh) has been shown to play a critical role in cognitive processes such as attention and learning. Previous research in animal models has shown that plasticity in sensory systems often depends on the task relevance of the stimulus, but experimentally increasing ACh in cortex can replace task relevance in inducing experience-dependent plasticity. Perceptual learning (PL) is a specific and persistent improvement in performance of a perceptual task with training. To test the role of ACh in PL of visual discrimination, we pharmacologically enhanced cholinergic transmission in the brains of healthy human participants by administering the cholinesterase inhibitor donepezil (trade name: Aricept), a commonly prescribed treatment for Alzheimer�s disease. To directly evaluate the effect of cholinergic enhancement, we conducted a double-blind, placebo-controlled cross-over study, in which each subject participated in a course of training under placebo and a course of training under donepezil. We found that, relative to placebo, donepezil increased the magnitude and specificity of the improvement in perceptual performance following PL. These results suggest that ACh plays a role in highlighting occasions in which learning should occur. Specifically, ACh may regulate neural plasticity by selectively increasing responses of neurons to behaviorally relevant stimuli.

Pharmacological Influences on Oculomotor Control in Healthy Humans

Ulrich Ettinger, Rheinische Friedrich-Wilhelms-Universit�t Bonn

Oculomotor control can be studied as an important model system for our understanding of how the brain implements visually informed (reflexive and voluntary) movements. A number of paradigms have been developed to investigate specific aspects of the cognitive and sensorimotor processes underlying this fascinating ability of the brain. For example, saccadic paradigms allow the specific and experimentally controlled study of response inhibition as well as temporo-spatial prediction. In this talk I will present recent data from studies investigating pharmacological influences on saccadic control in healthy humans. Findings from nicotine studies point to improvements of response inhibition and volitional response generation through this cholinergic agonist. Evidence from methylphenidate on the other hand suggests that oculomotor as well as motor response inhibition is unaffected by this dopaminergic manipulation, whereas the generation of saccades to temporally predictive visual targets is improved. These findings will be integrated with our published and ongoing work on the molecular genetic correlates of eye movements as well as their underlying brain activity. I will conclude by (1) summarising the pharmacological mechanisms underlying saccadic control and (2) emphasising the role that such oculomotor tasks may play in the evaluation of potential cognitive enhancing compounds, with implications for neuropsychiatric conditions such as ADHD, schizophrenia and dementia.

The effects of aging on GABAergic mechanisms and their influence on visual perception

Patrick J. Bennett and Allison B. Sekuler, Department of Psychology, Neuroscience & Behaviour McMaster University

The functional properties of visual mechanisms, such as the tuning properties of visual cortical neurons, are thought to emerge from an interaction among excitatory and inhibitory neural mechanisms. Hence, changing the balance between excitation and inhibition should lead, at least in some cases, to measurable changes in these mechanisms and, presumably, visual perception. Recent evidence suggests that aging is associated with changes in GABAergic signaling (Leventhal et al., 2003; Pinto et al., 2010), however it remains unclear how these changes manifest themselves in performance in psychophysical tasks. Specifically, some psychophysical studies (Betts et al., 2005; Wilson et al., 2011), but not all, are consistent with the idea that certain aspects of age-related changes in vision are caused by a reduction in the effectiveness of cortical inhibitory circuits. In my talk I will review the evidence showing that aging is related to changes in GABAergic mechanisms and the challenges associated with linking such changes to psychophysical performance.