Active avoidance learning is a complex form of aversive feedback learning that in humans and other animals is essential for actively coping with unpleasant, aversive, or dangerous situations. Since the functional circuits involved in two-way avoidance (TWA) learning have not yet been entirely identified, the aim of this study was to obtain an overall picture of the brain circuits that are involved in active avoidance learning. In order to obtain a longitudinal assessment of activation patterns in the brain of freely behaving rats during different stages of learning, we applied single-photon emission computed tomography (SPECT). We were able to identify distinct prefrontal cortical, sensory, and limbic circuits that were specifically recruited during the acquisition and retrieval phases of the two-way avoidance learning task.

Phobia against spiders or snakes is common in humans, and similar phobia-like behaviors have been observed in non-human animals. Visual images of snakes elicit phobia in humans, but sensory modalities that cause snake aversion in non-human animals are not well examined. In this study, we examined visually induced snake aversion in two rodent species. Using a three-compartment experimental chamber, reactions to images of snakes were compared between the diurnal precocious rodent Octodon degus and nocturnal laboratory mice. The snakes whose images were presented do not live in the original habitats of degus or mice. Snake aversion was assessed by presenting snake vs. no-image, snake vs. flower, snake vs. degu, and snake vs. mouse images. The time spent in a compartment with the snake image and with the non-snake images were measured. Degus avoided images of snakes in every tests. In contrast, mice did not display snake aversion. Degus are diurnal animals, i.e., visual information is important for their survival. Since mice are nocturnal, visual information is less important for survival. Such behavioral differences in the two species may explain the difference in visually induced aversion to snakes. A principal component analysis of the stimulus images suggests that elementary cues, such as color, do not explain the differences in the species' aversion to snakes. Finally, snake aversion in degus suggests that aversion is innate, since the animals were born and raised in a laboratory.

Multisensory integration in primary auditory (A1), visual (V1), and somatosensory cortex (S1) is substantially mediated by their direct interconnections and by thalamic inputs across the sensory modalities. We have previously shown in rodents (Mongolian gerbils) that during postnatal development, the anatomical and functional strengths of these crossmodal and also of sensory matched connections are determined by early auditory, somatosensory, and visual experience. Because supragranular layer III pyramidal neurons are major targets of corticocortical and thalamocortical connections, we investigated in this follow-up study how the loss of early sensory experience changes their dendritic morphology. Gerbils were sensory deprived early in development by either bilateral sciatic nerve transection at postnatal day (P) 5, ototoxic inner hair cell damage at P10, or eye enucleation at P10. Sholl and branch order analyses of Golgi-stained layer III pyramidal neurons at P28, which demarcates the end of the sensory critical period in this species, revealed that visual and somatosensory deprivation leads to a general increase of apical and basal dendritic branching in A1, V1, and S1. In contrast, dendritic branching, particularly of apical dendrites, decreased in all three areas following auditory deprivation. Generally, the number of spines, and consequently spine density, along the apical and basal dendrites decreased in both sensory deprived and non-deprived cortical areas. Therefore, we conclude that the loss of early sensory experience induces a refinement of corticocortical crossmodal and other cortical and thalamic connections by pruning of dendritic spines at the end of the critical period. Based on present and previous own results and on findings from the literature, we propose a scenario for multisensory development following early sensory loss.

Auditory perception is improved when stimuli are predictable, and this effect is evident in a modulation of the activity of neurons in the auditory cortex as shown previously. Human listeners can better predict the presence of duration deviants embedded in stimulus streams with fixed interonset interval (isochrony) and repeated duration pattern (regularity), and neurons in the auditory cortex of macaque monkeys have stronger sustained responses in the 60–140 ms post‐stimulus time window under these conditions. Subsequently, the question has arisen whether isochrony or regularity in the sensory input contributed to the enhancement of the neuronal and behavioural responses. Therefore, we varied the two factors isochrony and regularity independently and measured the ability of human subjects to detect deviants embedded in these sequences as well as measuring the responses of neurons the primary auditory cortex of macaque monkeys during presentations of the sequences. The performance of humans in detecting deviants was significantly increased by regularity. Isochrony enhanced detection only in the presence of the regularity cue. In monkeys, regularity increased the sustained component of neuronal tone responses in auditory cortex while isochrony had no consistent effect. Although both regularity and isochrony can be considered as parameters that would make a sequence of sounds more predictable, our results from the human and monkey experiments converge in that regularity has a greater influence on behavioural performance and neuronal responses.

Most nonhuman animals do not show selective preference for types of music, but researchers have typically employed only Western classical music in such studies. Thus, there has been bias in music choice. Degus (Octodon degus), originally from the mountain areas of Chile, have highly developed vocal communication. Here, we examined music preference of degus using not only Western classical music (music composed by Bach and Stravinsky), but also South American folk music (Chilean and Peruvian). The degus preferred the South American music to the Western classical music but did not show selective preference between the two Western classical music choices. Furthermore, the degus preferred the Chilean to the Peruvian music to some extent. In the second experiment, we examined preference for music vs. silence. Degus overall showed a preference for Chilean music over silence, but preferred silence over Western music. The present results indicate that the previous negative data for musical preference in nonhuman animals may be due to biased music selection (Krause, 2012). Our results suggest the possibility that the soundscape of an environment influences folk music created by native peoples living there and the auditory preference of other resident animals there.

Magnetic resonance imaging (MRI) at ultra-high fields (UHF), such as 7 T, provides an enhanced signal-to-noise ratio and has led to unprecedented high-resolution anatomic images and brain activation maps. Although a variety of radio frequency (RF) coil architectures have been developed for imaging at UHF conditions, they usually are specialized for small volumes of interests (VoI). So far, whole-body coil resonators are not available for commercial UHF human whole-body MRI systems. The goal of the present study was the development and validation of a transmit and receive system for large VoIs that operates at a 7 T human whole-body MRI system. A Metamaterial Ring Antenna System (MRAS) consisting of several ring antennas was developed, since it allows for the imaging of extended VoIs. Furthermore, the MRAS not only requires lower intensities of the irradiated RF energy, but also provides a more confined and focused injection of excitation energy on selected body parts. The MRAS consisted of several antennas with 50 cm inner diameter, 10 cm width and 0.5 cm depth. The position of the rings was freely adjustable. Conformal resonant right-/left-handed metamaterial was used for each ring antenna with two quadrature feeding ports for RF power. The system was successfully implemented and demonstrated with both a silicone oil and a water-NaCl-isopropanol phantom as well as in vivo by acquiring whole-body images of a crab-eating macaque. The potential for future neuroimaging applications was demonstrated by the acquired high-resolution anatomic images of the macaque's head. Phantom and in vivo measurements of crab-eating macaques provided high-resolution images with large VoIs up to 40 cm in xy-direction and 45 cm in z-direction. The results of this work demonstrate the feasibility of the MRAS system for UHF MRI as proof of principle. The MRAS shows a substantial potential for MR imaging of larger volumes at 7 T UHF. This new technique may provide new diagnostic potential in spatially extended pathologies such as searching for spread-out tumor metastases or monitoring systemic inflammatory processes.

We address the question of whether the auditory cortex of the left and right hemisphere and the auditory thalamus are differently involved in the performance of cognitive tasks. To understand these differences on the level of single neurons we compared neuronal firing in the primary and posterior auditory cortex of the two hemispheres and in the medial geniculate body in monkeys while subjects categorized pitch relationships in tone sequences. In contrast to earlier findings in imaging studies performed on humans, we found little difference between the three brain regions in terms of the category-specificity of their neuronal responses, of tonic firing related to task components, and of decision-related firing. The differences between the results in humans and monkeys may result from the type of neuronal activity considered and how it was analyzed, from the auditory cortical fields studied, or from fundamental differences between these species.

This study shows that ongoing electrical stimulation of the dopaminergic ventral midbrain can modify neuronal activity in the auditory cortex of awake primates for several seconds. This was reflected in a decrease of the spontaneous firing and in a bidirectional modification of the power of auditory evoked potentials. We consider that both effects are due to an increase in the dopamine tone in auditory cortex induced by the electrical stimulation. Thus, the dopaminergic ventral midbrain may contribute to the tonic activity in auditory cortex that has been proposed to be involved in associating events of auditory tasks (Brosch et al. Hear Res 271:66–73, 2011) and may modulate the signal-to-noise ratio of the responses to auditory stimuli.

This study aimed at a deeper understanding of which cognitive and motivational aspects of tasks affect auditory cortical activity. To this end we trained two macaque monkeys to perform two different tasks on the same audiovisual stimulus and to do this with two different sizes of water rewards. The monkeys had to touch a bar after a tone had been turned on together with an LED, and to hold the bar until either the tone (auditory task) or the LED (visual task) was turned off. In 399 multiunits recorded from core fields of auditory cortex we confirmed that during task engagement neurons responded to auditory and non-auditory stimuli that were task-relevant, such as light and water. We also confirmed that firing rates slowly increased or decreased for several seconds during various phases of the tasks. Responses to non-auditory stimuli and slow firing changes were observed during both the auditory and the visual task, with some differences between them. There was also a weak task-dependent modulation of the responses to auditory stimuli. In contrast to these cognitive aspects, motivational aspects of the tasks were not reflected in the firing, except during delivery of the water reward. In conclusion, the present study supports our previous proposal that there are two response types in the auditory cortex that represent the timing and the type of auditory and non-auditory elements of a auditory tasks as well the association between elements.

It is commonly assumed that cortical activity in non-rapid eye movement sleep (NREMS) is spatially homogeneous on the mesoscopic scale. This is partly due to the limited observational scope of common metabolic or imaging methods in sleep. We used the recently developed technique of thallium-autometallography (TlAMG) to visualize mesoscopic patterns of activity in the sleeping cortex with single-cell resolution. We intravenously injected rats with the lipophilic chelate complex thallium diethyldithiocarbamate (TlDDC) during spontaneously occurring periods of NREMS and mapped the patterns of neuronal uptake of the potassium (K+) probe thallium (Tl+). Using this method, we show that cortical activity patterns are not spatially homogeneous during discrete 5-min episodes of NREMS in unrestrained rats—rather, they are complex and spatially diverse. Along with a relative predominance of infragranular layer activation, we find pronounced differences in metabolic activity of neighboring neuronal assemblies, an observation which lends support to the emerging paradigm that sleep is a distributed process with regulation on the local scale.

Motivated by the increasing evidence that auditory cortex is under control of dopaminergic cell structures of the ventral midbrain, we studied how the ventral tegmental area and substantia nigra affect neuronal activity in auditory cortex. We electrically stimulated 567 deep brain sites in total within and in the vicinity of the two dopaminergic ventral midbrain structures and at the same time, recorded local field potentials and neuronal discharges in cortex. In experiments conducted on three awake macaque monkeys, we found that electrical stimulation of the dopaminergic ventral midbrain resulted in short-latency (~35 ms) phasic activations in all cortical layers of auditory cortex. We were also able to demonstrate similar activations in secondary somatosensory cortex and superior temporal polysensory cortex. The electrically evoked responses in these parts of sensory cortex were similar to those previously described for prefrontal cortex. Moreover, these phasic responses could be reversibly altered by the dopamine D1-receptor antagonist SCH23390 for several tens of minutes. Thus, we speculate that the dopaminergic ventral midbrain exerts a temporally precise, phasic influence on sensory cortex using fast-acting non-dopaminergic transmitters and that their effects are modulated by dopamine on a longer timescale. Our findings suggest that some of the information carried by the neuronal discharges in the dopaminergic ventral midbrain, such as the motivational value or the motivational salience, is transmitted to auditory cortex and other parts of sensory cortex. The mesocortical pathway may thus contribute to the representation of non-auditory events in the auditory cortex and to its associative functions.

From September 13 to 17, 2014, more than 270 auditory neuroscientists from 24 countries gathered in Magdeburg (Germany) for the 5th International Conference on Auditory Cortex (www.auditory-cortex.de), which was hosted by the Leibniz Institute for Neurobiology in Magdeburg. This conference continued a series of previous conferences held in Magdeburg in 2003 and 2009, in Grantham (UK) in 2006, and in Lausanne (Switzerland) in 2012. This Special Issue of the European Journal of Neuroscience (EJN) brings together 17 peer-reviewed papers nearly all based on invited talks presented at this meeting. The abstracts of all 200 contributions (40 invited speakers, 160 posters) can be found in the “Proceedings of the 5th International Conference on Auditory Cortex – Towards a Synthesis of Human and Animal Research” (Budinger, 2014). Sometime in 2002, Henning Scheich, one of the most influential contemporary German neuroscientists and founding director of the Leibniz Institute for Neurobiology in Magdeburg, expressed the idea that it was about time to bring together scientists working on the auditory cortex of humans with those working on that part of the brain in animals. An international meeting would enable these scientists to learn and benefit from each other's knowledge and experience by exchanging concepts, approaches, and thoughts. The researchers studying the human auditory cortex, mainly using non-invasive techniques such as functional magnetic resonance imaging, magneto- and electroencephalography, often seemed rather unaware of the progress made by the researchers studying the auditory cortices of animals, mainly using invasive anatomical and physiological methods; and vice versa. Henning Scheich's idea fell on fertile grounds and, after a short survey among several local and outside experts, the ICAC was born. In 2003, more than 200 participants from all over the world attended the first ICAC in Magdeburg, hosted by the Leibniz Institute for Neurobiology. Taking up Henning Scheich's idea, it consequently carried the subtitle “Towards a Synthesis of Human and Animal Research”. The conference agenda covered three main themes: (i) auditory cortical fields and their functions, (ii) coding of sounds, and (iii) plasticity, learning, and cognition (Budinger & Gaschler-Markefski, 2003). The presentations of the 35 invited talks and more than 100 posters were excellent, the discussions were lively, and the social events facilitated the communication between the participants. The scientific outcome resulted in the publication of the 500-page book “The Auditory Cortex – A Synthesis of Human and Animal Research” (König et al., 2005). The success of this first conference triggered a second one; in fact, it started a series. In 2006, the second conference took place in Grantham, east of Nottingham (UK). It was organized by Dave Moore, Alan Palmer, Deborah Hall, Chris Sumner, Lisa Fretwell, Angie Killoran, and colleagues of the MRC Institute of Hearing Research. The meeting was subtitled “The Listening Brain” to indicate both the importance of active engagement with acoustic signals, an issue that has already emerged from the 2003 meeting, and the advances that had been made in understanding the role of the auditory cortex in “active hearing” or “listening”. Some 160 participants discussed the 20 invited talks and 80 posters, which covered three main topics: (i) the distributed, (ii) the computational, and (iii) the cognitive auditory cortex. Papers related to these and other topics of the conference appeared in a Special Issue of Hearing Research (see Moore et al., 2007). Returning to Magdeburg, the subtitle of the 2009 conference “Current Concepts in Human and Animal Research” again reflected our main goal: to bring together scientists who study the auditory cortex in humans with those who study it in animals. The conference was arranged around five sessions comprising 33 invited talks: (i) how to define auditory cortex, (ii) coding principles in the auditory cortex, (iii) the adaptive auditory cortex, (iv) processing of vocalizations, speech, and music, and (v) functional circuitry in the auditory cortex. During a round table discussion, seven renowned experts contrasted concepts of auditory functions together with 200 attendees. About 120 posters, some also advertised in short oral presentations, completed the scientific program. A collection of papers based on the invited talks of the conference was again published in a Special Issue of Hearing Research (see Brechmann et al., 2011). In 2012, the scientific organizers of the fourth conference (Daphne Bavelier, Stephanie Clarke, Jonathan Fritz, Troy Hackett, Andrew King, Micah Murray, David Poeppel, Shihab Shamma, Mark Wallace) in Lausanne (Switzerland) decided arranging the meeting on the basis of submitted proposals for scientific symposia. The five proposals winning the competition were: (i) integrating behavior and neurophysiology, (ii) dynamic spatial processing in the auditory cortex, (iii) shedding light on auditory cortex, (iv) computational principles of auditory cortex, and (v) perceptual operations and underlying mechanisms in the primate auditory cortices. These five symposia comprised 23 talks and were complemented by a graduate students' award symposium, a moderated (heated) debate, and about 170 posters. In March 2015, some of the contributions will be available as papers in a Special Issue of Brain Topography (Vol. 28/2). In order to avoid temporal overlap with the International Symposium on Hearing, it was agreed upon to deviate from the 3-year interval and to hold the fifth meeting already in 2014, again in Magdeburg (see below). In 2017, the 6th ICAC will take place in Banff (Canada), and it is organized by Stephen Lomber from the University of Western Ontario (Canada) and Yale Cohen from the University of Pennsylvania (USA). It is planned that three years later the conference will return to Magdeburg. The subtitle of the 5th International Conference on Auditory Cortex was again “Towards a Synthesis of Human and Animal Research” because of the continued need to join the two fields. The scientific program reflected current topics studied in both fields and was arranged around the following six sessions: (i) auditory cortex in different species, (ii) the hearing action cycle, (iii) auditory cortex: it's about time, (iv) auditory cortex: clinical aspects, (v) multisensory interplay in auditory cortex, and (vi) learning in auditory cortex. Invited speakers from each of these sessions agreed to contribute to this Special Issue of the EJN. Their papers are reviews, opinions as well as original research based on the presentations at the meeting; however, they also elaborate beyond what was presented there. Studies of the anatomical and functional organization of auditory cortex in different species (topic i) and its role in communication and behavior help to identify common underlying principles of auditory cortex functioning and to distinguish them from species-specific specializations owing to particular needs and evolutionary traits. They also emphasize the value of neuroethological approaches for understanding auditory behavior, including vocal communication. Kössl et al. evaluate in which respect the processing modules of bat auditory cortex can serve as a model for typical mammalian auditory-cortex function or are suited for purposes unique to the demands imposed by echolocation, such as estimating range from echo delays. Wallmeier et al. explore the role of auditory and visual cortex in humans during echolocation tasks. Their fMRI data show that early-blind echolocation experts and sighted, echolocation-trained control subjects, recruit different cortical areas for the same active-echolocation task. Elie & Theunissen investigate the neural representation of the semantic categories of zebra finch vocalizations within primary and secondary auditory cortical areas, showing that computations necessary for semantic categorization of meaningful vocalization are present in the avian auditory cortex. Wilson et al. used rule-based sequences of sounds, with local and longer-distance relationships, to study artificial grammar learning in nonhuman primates and in humans. Their results suggest that the required sequence-processing computations may not be unique to language-possessing humans. Rauschecker argues that an improved understanding of auditory cortical processing can be obtained by comparison to visual cortical functioning, on both a level of neural mechanism and of processing pathways for the identification of objects and the processing of space. Furthermore, expanding this idea in terms of sensorimotor integration and control would provide an overarching view of cortical function independent of sensory modality. When we hear sounds we may decide to orient and act towards the location from where the sounds originate. When we move we frequently generate sounds, and we use sounds to guide and control our movements and actions. The interrelationships between sounds and actions have recently come into the focus of interest of researchers of auditory cortex. They complement recent research on the representation of non-auditory aspects of auditory tasks in auditory cortex. They also complement the notion that auditory cortex functions as a “semantic processor” deducing the task-specific meaning of sounds. In this Special Issue, we were able to attract two groups of authors (Merchant et al. and Brosch et al.) to contribute articles to aspects of this hearing-action cycle (topic ii). Time is most essential (topic iii) for processing of auditory-related information. Neurons in the auditory cortex are sensitive to aspects of sounds on multiple time scales, from a few milliseconds up to several seconds. In this way, neurons possibly encode the complexity of past auditory stimulation, and this attribute may also play a crucial role in the prediction of upcoming auditory events. Issues derived from studies on humans and animals and related to the representation and the relevance of time comprised stimulus specific adaptation, temporal structure of sound sequences, cortical dynamics of speech perception and language comprehension, inhibitory networks and functional processing of spectral and temporal response features, temporal dynamics and spatial distribution of high gamma activity, and predictive processing. May et al. contribute a paper to this Special Issue, in which, based on computational modeling, the relevance of long-term synaptic adaptation for temporal integration in auditory cortex is addressed. Schroeger et al. review what can be learned from cognitive psychophysiology about prediction and attention in audition and discuss these two concepts in the framework of the predictive coding theory. König et al. scrutinize the averaging process in MEG/EEG research and emphasize that the common practice of subtracting arithmetic means of auditory-evoked waveforms is problematic. They encourage researchers to check which model (additive or mixed) underlies their data and to apply an appropriate transform, the asinh-transformation, if required. Apart from the gap between animal and human research, another gap needs to be bridged, namely that between fundamental and clinical research (topic iv). Three major clinical topics in auditory research are auditory-based language impairments, restorations of hearing by cochlear implants, and tinnitus. Here, Eggermont provides an overview of the achievements in tinnitus research both on animals and humans and importantly addresses the question about how predictions from animals models relate to findings in human cochlear implant users. Strelnikov et al. present results of a PET study on cochlear implant users that provide insights into experience dependent plasticity effects in audio-visual integration. Such research will hopefully arouse more interest in clinical aspects of auditory functions; both to transfer knowledge from basic research into the clinic and to better understand normal auditory processing. The problems of how the different senses merge in the brain and how the brain associates this information with behavioral demands have kept neuroscientists busy for several decades. Initially, research focused on “classical” multisensory brain structures like the superior colliculus and the parietal cortex; recent research also includes low-level cortical areas, previously deemed unisensory. In this Special Issue, authors from various fields of animal and human research present their scientific results and views on the role of the auditory cortex in multisensory processing (topic v). They emphasize, for example, specific functions of the different auditory fields and other brain areas in audiovisual and audiotactile integration processes, physiological mechanisms and anatomical pathways of multisensory integration at cellular and areal levels (Meredith & Allman; Brosch et al.), the role of single- and multi-trial learning (Matusz et al.; Brosch et al.) as well as short- and long-term musical training (Pantev et al.) on the neuronal processing of uni- and multisensory information, and mechanisms of cross-modal reorganizations following sensory impairment and restoration (Meredith & Allman; Strelnikov et al.). Quite generally, neurobiological research on learning (topic vi) has to bridge a categorical gap because learning is a phenomenon defined on the behavioral and psychological level. In auditory cortex research, the identification of potential neural mechanisms underlying specific alterations of behavior or psychophysical performance induced by learning has been particularly successful. In this Special Issue, authors (Bao; Perks & Gentner; Pantev et al.) report and discuss recent findings of physiological mechanisms underlying learning and learning-related phenomena on multiple levels, ranging from cellular physiology, via neural network dynamics and imaging results to particular behaviors in rodents, birds, and humans. We wish to thank the many sponsors of our meeting, most notably the Deutsche Forschungsgemeinschaft, the Office of Naval Research Global, the Magdeburg Center for Behavioral Brain Sciences, and, of course, the host of the meeting, the Leibniz Institute for Neurobiology Magdeburg; for a complete list of sponsors see www.auditory-cortex.de/sponsors.html. We are most grateful to Carola Kolouschek (Public Relations|Media|Events, Magdeburg) for the administrative organization of the conference, to the Herrenkrug Parkhotel for providing the outstanding ambience, and to all the people who provided a helping hand before, during, and after the conference (all listed under www.auditory-cortex.de/acknowledgements.html). We would also like to thank the authors and anonymous reviewers of the papers of this Special Issue and the EJN staff, in particular Sophie Gavarini, Julie Mion, Martin Sarter, and Jean-Marc Fritschy, who took all editorial handling and decisions, thus enforcing the timely publication of this Special Issue. Finally, we would like to thank all participants, for coming to Magdeburg to join the conference and contribute to its sessions; thus, filling the scientific as well as the social events with life. The scientific organizing committee and guest editors of this Special Issue of EJN: André Brechmann, Michael Brosch, Eike Budinger, Peter Heil, Reinhard König, Frank Ohl, and Henning Scheich. Magdeburg, December 23, 2014.

Multisensory integration does not only recruit higher-level association cortex, but also low-level and even primary sensory cortices. Here, we will describe and quantify two types of anatomical pathways, a thalamocortical and a corticocortical that possibly underlie short-latency multisensory integration processes in the primary auditory (A1), somatosensory (S1), and visual cortex (V1). Results were obtained from Mongolian gerbils, a common model-species in neuroscience, using simultaneous injections of different retrograde tracers into A1, S1, and V1. Several auditory, visual, and somatosensory thalamic nuclei project not only to the primary sensory area of their own (matched) but also to areas of other (non-matched) modalities. The crossmodal output ratios of these nuclei, belonging to both core and non-core sensory pathways, vary between 0.4 and 63.5 % of the labeled neurons. Approximately 0.3 % of the sensory thalamic input to A1, 5.0 % to S1, and 2.1 % to V1 arise from non-matched nuclei. V1 has most crossmodal corticocortical connections, projecting strongest to S1 and receiving a similar amount of moderate inputs from A1 and S1. S1 is mainly interconnected with V1. A1 has slightly more projections to V1 than S1, but gets just faint inputs from there. Concerning the layer-specific distribution of the retrogradely labeled somata in cortex, V1 provides the most pronounced feedforward-type outputs and receives (together with S1) most pronounced feedback-type inputs. In contrast, A1 has most pronounced feedback-type outputs and feedforward-type inputs in this network. Functionally, the different sets of thalamocortical and corticocortical connections could underlie distinctive types of integration mechanisms for different modality pairings.

BACKGROUND:Since the mesocortical dopaminergic system of rodents has several differences to that found in primate species, including humans, there is the need for more exhaustively studying causative relationships between activation/stimulation of the ventral tegmental area (VTA) and substantia nigra (SN) and behavior in monkeys.OBJECTIVE:To gain causative relationships between VTA/SN stimulation and behavior, we investigated whether monkeys perform audiovisual (AV) tasks using brain stimulation reward (BSR) as the reinforcer, and how reward intensity affects performance during self-stimulation.METHODS:Monkeys were required to touch a bar freely when self-stimulating or when instructed by an AV stimulus, to receive BSR.RESULTS:We were able to train monkeys to successfully perform the AV task for BSR within three days. Self-stimulation revealed an increase in the bar touch rate when using higher electrical currents, with no ceiling effects observed. During a training session the touch rate decreased, often before the monkeys had received 1000 deliveries of BSR, suggesting satiation.CONCLUSIONS:When BSR is applied directly to the VTA/SN, it can motivate monkeys to perform detection tasks, exhibit operant actions, and may be used as a substitute for fluid or food rewards. Monkeys ceased self-stimulation during a training session by their own volition, in contrast to work on rodents. This may be an important safety aspect for consideration in the development of electrical stimulation procedures for patients with dysfunctions of the dopaminergic system; thus, satiation may avert additional compulsions to already existing compulsive behaviors in patients.

Electrical and optogenetic methods for brain stimulation are widely used in rodents for manipulating behavior and analyzing functional connectivities in neuronal circuits. High-resolution in vivo imaging of the global, brain-wide, activation patterns induced by these stimulations has remained challenging, in particular in awake behaving mice. We here mapped brain activation patterns in awake, intracranially self-stimulating mice using a novel protocol for single-photon emission computed tomography (SPECT) imaging of regional cerebral blood flow (rCBF). Mice were implanted with either electrodes for electrical stimulation of the medial forebrain bundle (mfb-microstim) or with optical fibers for blue-light stimulation of channelrhodopsin-2 expressing neurons in the ventral tegmental area (vta-optostim). After training for self-stimulation by current or light application, respectively, mice were implanted with jugular vein catheters and intravenously injected with the flow tracer 99m-technetium hexamethylpropyleneamine oxime (99mTc-HMPAO) during seven to ten minutes of intracranial self-stimulation or ongoing behavior without stimulation. The 99mTc-brain distributions were mapped in anesthetized animals after stimulation using multipinhole SPECT. Upon self-stimulation rCBF strongly increased at the electrode tip in mfb-microstim mice. In vta-optostim mice peak activations were found outside the stimulation site. Partly overlapping brain-wide networks of activations and deactivations were found in both groups. When testing all self-stimulating mice against all controls highly significant activations were found in the rostromedial nucleus accumbens shell. SPECT-imaging of rCBF using intravenous tracer-injection during ongoing behavior is a new tool for imaging regional brain activation patterns in awake behaving rodents providing higher spatial and temporal resolutions than 18F-2-fluoro-2-dexoyglucose positron emission tomography.