Malgorzata Kossut

Somatostatin and Somatostatin-Containing Neurons in Shaping Neuronal Activity and Plasticity.

Since its discovery over four decades ago, somatostatin (SOM) receives growing scientific and clinical interest. Being localized in the nervous system in a subset of interneurons somatostatin acts as a neurotransmitter or neuromodulator and its role in the fine-tuning of neuronal activity and involvement in synaptic plasticity and memory formation are widely recognized in the recent literature. Combining transgenic animals with electrophysiological, anatomical and molecular methods allowed to characterize several subpopulations of somatostatin-containing interneurons possessing specific anatomical and physiological features engaged in controlling the output of cortical excitatory neurons. Special characteristic and connectivity of somatostatin-containing neurons set them up as significant players in shaping activity and plasticity of the nervous system. However, somatostatin is not just a marker of particular interneuronal subpopulation. Somatostatin itself acts pre- and postsynaptically, modulating excitability and neuronal responses. In the present review, we combine the knowledge regarding somatostatin and somatostatin-containing interneurons, trying to incorporate it into the current view concerning the role of the somatostatinergic system in cortical plasticity.

Circadian rhythmicity of synapses in mouse somatosensory cortex.

The circadian rhythmicity displayed by motor behavior of mice: activity at night and rest during the day; and the associated changes in the sensory input are reflected by cyclic synaptic plasticity in the whisker representations located in the somatosensory (barrel) cortex. It was not clear whether diurnal rhythmic changes in synapse density previously observed in the barrel cortex resulted from changes in the activity of the animals, from daily light/dark (LD) rhythm or are driven by an endogenous clock. These changes were investigated in the barrel cortex of C57BL/6 mouse strain kept under LD 12 : 12 h conditions and in constant darkness (DD). Stereological analysis of serial electron microscopic sections was used to assess numerical density of synapses. In mice kept under LD conditions, the total density of synapses and the density of excitatory synapses located on dendritic spines was higher during the light period (rest phase). In contrast, the density of inhibitory synapses located on dendritic spines increased during the dark period (activity phase). Under DD conditions, the upregulation of the inhibitory synapses during the activity phase was retained, but the cyclic changes in the density of excitatory synapses were not observed. The results show that the circadian plasticity concerns only synapses located on spines (and not those on dendritic shafts), and that excitatory and inhibitory synapses are differently regulated during the 24 h cycle: the excitatory synapses are influenced by light, whilst the inhibitory synapses are driven by the endogenous circadian clock.

Functional and Structural Neuroplasticity Induced by Short-Term Tactile Training Based on Braille Reading.

Neuroplastic changes induced by sensory learning have been recognized within the cortices of specific modalities as well as within higher ordered multimodal areas. The interplay between these areas is not fully understood, particularly in the case of somatosensory learning. Here we examined functional and structural changes induced by short-term tactile training based of Braille reading, a task that requires both significant tactile expertise and mapping of tactile input onto multimodal representations. Subjects with normal vision were trained for 3 weeks to read Braille exclusively by touch and scanned before and after training, while performing a same-different discrimination task on Braille characters and meaningless characters. Functional and diffusion-weighted magnetic resonance imaging sequences were used to assess resulting changes. The strongest training-induced effect was found in the primary somatosensory cortex (SI), where we observed bilateral augmentation in activity accompanied by an increase in fractional anisotropy (FA) within the contralateral SI. Increases of white matter fractional anisotropy were also observed in the secondary somatosensory area (SII) and the thalamus. Outside of somatosensory system, changes in both structure and function were found in i.e., the fusiform gyrus, the medial frontal gyri and the inferior parietal lobule. Our results provide evidence for functional remodeling of the somatosensory pathway and higher ordered multimodal brain areas occurring as a result of short-lasting tactile learning, and add to them a novel picture of extensive white matter plasticity.

Design and evaluation of an innovative MRI-compatible Braille stimulator with high spatial and temporal resolution.

Neural correlates of Braille reading have been widely studied with different neuroimaging techniques. Nevertheless, the exact brain processes underlying this unique activity are still unknown, due to suboptimal accuracy of imaging and/or stimuli delivery methods. To study somatosensory perception effectively, the stimulation must reflect parameters of the natural stimulus and must be applied with precise timing. In functional magnetic resonance imaging (fMRI) providing these characteristics requires technologically advanced solutions and there have been several successful direct tactile stimulation devices designed that allow investigation of somatotopic organization of brain sensory areas. They may, however, be of limited applicability in studying brain mechanisms related to such distinctive tactile activity as Braille reading. In this paper we describe the design and experimental evaluation of an innovative MRI-compatible Braille Character Stimulator (BCS) enabling precise and stable delivery of standardized Braille characters with high temporal resolution. Our device is fully programmable, flexible in stimuli delivery and can be easily implemented in any research unit. The Braille Character Stimulator was tested with a same-different discrimination task on Braille characters during an event-related fMRI experiment in eleven right-handed sighted adult subjects. The results show significant activations in several cortical areas, including bilateral primary (SI) and secondary somatosensory (SII) cortices, bilateral premotor and supplementary motor areas, inferior frontal gyri, inferior temporal gyri and precuneus, as well as contralateral (to the stimulated hand) thalamus. The results validate the use of the BCS as a method of effective stimuli application in fMRI studies, in both sighted and visually impaired subjects.

A causal role for right frontopolar cortex in directed, but not random, exploration

The explore-exploit dilemma occurs anytime we must choose between exploring unknown options for information and exploiting known resources for reward. Previous work suggests that people use two different strategies to solve the explore-exploit dilemma: directed exploration, driven by information seeking, and random exploration, driven by decision noise. Here, we show that these two strategies rely on different neural systems. Using transcranial magnetic stimulation to inhibit the right frontopolar cortex, we were able to selectively inhibit directed exploration while leaving random exploration intact. This suggests a causal role for right frontopolar cortex in directed, but not random, exploration and that directed and random exploration rely on (at least partially) dissociable neural systems.

Effect of Frustration on Brain Activation Pattern in Subjects with Different Temperament

In spite of the prevalence of frustration in everyday life, very few neuroimaging studies were focused on this emotional state. In the current study we aimed to examine effects of frustration on brain activity while performing a well-learned task in participants with low and high tolerance for arousal. Prior to the functional magnetic resonance imaging session, the subjects underwent 2 weeks of Braille reading training. Frustration induction was obtained by using a novel highly difficult tactile task based on discrimination of Braille-like raised dots patterns and negative feedback. Effectiveness of this procedure has been confirmed in a pilot study using galvanic skin response and questionnaires. Brain activation pattern during tactile discrimination task before and after frustration were compared directly. Results revealed changes in brain activity in structures mostly reported in acute stress studies: striatum, cingulate cortex, insula, middle frontal gyrus and precuneus and in structures engaged in tactile Braille discrimination: SI and SII. Temperament type affected activation pattern. Subjects with low tolerance for arousal showed higher activation in the posterior cingulate gyrus, precuneus, and inferior parietal lobule than high reactivity group. Even though performance in the discrimination trials following frustration was unaltered, we observed increased activity of primary and secondary somatosensory cortex processing the tactile information. We interpret this effect as an indicator of additional involvement required to counteract the effects of frustration.

Application of the DREADD technique in biomedical brain research

The DREADD (Designer Receptors Exclusively Activated by Designer Drugs) technique is a new chemogenetic approach allowing for selective and remote control of neural activity with a high degree of spatial resolution. Since its discovery in 2007 the DREADD technique was successfully employed into basic research, and together with the optogenetic method provided so far the best tool to influence the activity of the brain circuits and cell populations. The first aim of this review was to concisely describe the technique with regard to such issues like the history of its development, biochemistry as well as modes of the designer receptors delivery and expression. The other aim was to summarize approaches employed for probing of the brain circuits using the DREADD technique and to characterize the current knowledge of the methods application in medical research focusing on two diseases - Parkinsons disease and drug addiction - in which designer receptors were found notably valuable.

Age-Related Changes in Resting-State EEG Activity in Attention Deficit/Hyperactivity Disorder: A Cross-Sectional Study

Numerous studies indicate that attention deficit/hyperactivity disorder (ADHD) is related to some developmental trends, as its symptoms change widely over time. Nevertheless, the etiology of this phenomenon remains ambiguous. There is a disagreement whether ADHD is related to deviations in brain development or to a delay in brain maturation. The model of deviated brain development suggests that the ADHD brain matures in a fundamentally different way, and does not reach normal maturity at any developmental stage. On the contrary, the delayed brain maturation model assumes that the ADHD brain indeed matures in a different, delayed way in comparison to healthy age-matched controls, yet eventually reaches proper maturation. We investigated age-related changes in resting-state EEG activity to find evidence to support one of the alternative models. A total of 141 children and teenagers participated in the study; 67 diagnosed with ADHD and 74 healthy controls. The absolute power of delta, theta, alpha, and beta frequency bands was analyzed. We observed a significant developmental pattern of decreasing absolute EEG power in both groups. Nonetheless, ADHD was characterized by consistently lower absolute EGG power, mostly in the theta frequency band, in comparison to healthy controls. Our results are in line with the deviant brain maturation theory of ADHD, as the observed effects of age-related changes in EEG power are parallel but different in the two groups.

Correlated activation of the thalamocortical network in a simple learning paradigm.

The thalamocortical loop is a key player in sensory processing. We examined the functional interactions among its elements, expressed as cross-correlations between metabolic activity of the barrel cortex, somatosensory thalamic nuclei and posterior parietal cortex, in classical conditioning. In the training stimulation of vibrissae in mice was paired with a tail shock. [14C]-2-Deoxyglucose brain mapping was performed during the first and the final sessions of conditioning (conditioned stimulus+unconditioned stimulus; CS+UCS), in groups that received only the stimulation of vibrissae (conditioned stimulus; CS-only) and in nonstimulated controls (NS). In the CS-only group, the CS evoked the correlated activity of the examined structures during the first session, but in the third session these structures did not act in a correlated manner. Conversely, in the CS+UCS condition correlations among the thalamocortical loop structures activities became stronger during the course of the training. Particularly, the posterior parietal cortex, which controls voluntary deployment of attention, together with the barrel cortex becomes involved in the network of structures with the correlated activity. The results suggest a predominant role for bottom-up processing in the somatosensory pathway at the beginning of conditioning followed by top-down processing. This is consistent with the idea that the thalamocortical loop plays a crucial role in attentional processes.

Real-time strategy video game experience and structural connectivity - A diffusion tensor imaging study

Experienced video game players exhibit superior performance in visuospatial cognition when compared to non‐players. However, very little is known about the relation between video game experience and structural brain plasticity. To address this issue, a direct comparison of the white matter brain structure in RTS (real time strategy) video game players (VGPs) and non‐players (NVGPs) was performed. We hypothesized that RTS experience can enhance connectivity within and between occipital and parietal regions, as these regions are likely to be involved in the spatial and visual abilities that are trained while playing RTS games. The possible influence of long‐term RTS game play experience on brain structural connections was investigated using diffusion tensor imaging (DTI) and a region of interest (ROI) approach in order to describe the experience‐related plasticity of white matter. Our results revealed significantly more total white matter connections between occipital and parietal areas and within occipital areas in RTS players compared to NVGPs. Additionally, the RTS group had an altered topological organization of their structural network, expressed in local efficiency within the occipito‐parietal subnetwork. Furthermore, the positive association between network metrics and time spent playing RTS games suggests a close relationship between extensive, long‐term RTS game play and neuroplastic changes. These results indicate that long‐term and extensive RTS game experience induces alterations along axons that link structures of the occipito‐parietal loop involved in spatial and visual processing.