Neuromodulators such as acetylcholine and dopamine are able to rapidly reprogram neuronal information processing and dynamically change brain states. Degeneration or dysfunction of cholinergic and dopaminergic neurons can lead to neuropsychiatric conditions like schizophrenia and addiction or cognitive diseases such as Alzheimer’s. Neuromodulatory systems control overlapping cognitive processes and often have similar modes of action; therefore it is important to reveal cooperation and competition between different systems to understand their unique contributions to cognitive functions like learning, memory and attention. This is only possible by direct comparison, which necessitates monitoring multiple neuromodulatory systems under identical experimental conditions. Moreover, simultaneous recording of different neuromodulatory cell types goes beyond phenomenological description of similarities and differences by revealing the underlying correlation structure at the level of action potential timing. However, such data allowing direct comparison of neuromodulatory actions are still sparse. As a first step to bridge this gap, I propose to elucidate the unique versus complementary roles of two “classical” neuromodulatory systems, the cholinergic and dopaminergic projection system implicated in various cognitive functions including associative learning and plasticity. First, we will record optogenetically identified cholinergic and dopaminergic neurons simultaneously using chronic extracellular recording in mice undergoing classical and operant conditioning. Second, we will determine the postsynaptic impact of cholinergic and dopaminergic neurons by manipulating them both separately and simultaneously while recording consequential changes in cortical neuronal activity and learning behaviour. These experiments will reveal how major neuromodulatory systems interact to mediate similar or different aspects of the same cognitive functions.

Parkinson’s disease is dominated by motor symptoms such as tremor, bradykinesia and postural instability. However, over 90% of all patients develop cognitive impairment including deterioration of learning, memory and decision making. Current treatments focus on motor symptoms and offer at best moderate improvement of cognitive functions. Alleviating cognitive symptoms could dramatically increase quality of life of patients. Therefore, we propose to apply a behavioral test of fine decision making combined with electroencephalography and electromyography measurements to quantitatively assess complex aspects of cognitive function, including inhibitory control, learning by reinforcement and decision making under conflict. This Quantitative Cognitive Testing (QCT) can be employed to improve Parkinson’s disease therapy based on regular feedback. Moreover, the method can be extended to other domains of neurodegenerative dementias. We foresee that the application of QCT can facilitate the development of telemedicine packages, thus reducing hospital visits and patient-doctor contacts. Under this PoC, we propose to validate equipment we developed de novo, conduct proof of concept experiments, extend IPR protection, and explore commercialization strategies. We believe that QCT can help achieve the best possible cognitive function, which would improve the quality of life of patients and their families. It could also reduce disease-related cost burden on health care systems and society, making it appealing to health providers.

We will reveal the neuronal mechanisms of fundamental hippocampal and axonal functions using direct patch clamp recordings from the small axon terminals of the major glutamatergic afferent and efferent pathways of the dentate gyrus region. Specifically, we will investigate the intrinsic axonal properties and unitary synaptic functions of the axons in the dentate gyrus that originate from the entorhinal cortex, the hilar mossy cells and the hypothalamic supramammillary nucleus. The fully controlled access to the activity of individual neuronal projections allows us to address the crucial questions how upstream regions of the dentate gyrus convey physiologically relevant spike activities and how these activities are translated to unitary synaptic responses in individual dentate gyrus neurons. The successful information transfers by these mechanisms ultimately generate specific dentate gyrus cell activity that contributes to hippocampal memory functions. Comprehensive mechanistic insights are essential to understand the impacts of the activity patterns associated with fundamental physiological functions and attainable with the necessary details only with direct recordings from individual axons. For example, these knowledge are necessary to understand how single cell activities in the entorhinal cortex (carrying primary spatial information) contribute to spatial representation in the dentate (i.e. place fields). Furthermore, because the size of these recorded axon terminals matches that of the majority of cortical synapses, our discoveries will demonstrate basic biophysical and neuronal principles of axonal signaling that are relevant for universal neuronal functions throughout the CNS. Thus, an exceptional repertoire of methods, including recording from anatomically identified individual small axon terminals, voltage- and calcium imaging and computational simulations, places us in an advantaged position for revealing unprecedented information about neuronal circuits.

Wheat the most important food crop in Europe with an increasing demand to preserve its production potential to ensure long-term food security. However, wheat is facing such challenges as climate change and the severe genetic bottleneck of cultivated wheat imposed by domestication, cannot surmount such difficulties. Wheat landraces are better adapted than modern cultivars to changing climate conditions and to stress environments. The conservation and effective management of crop diversity are thus essential to prepare future plant cultivars to the effects of climate change. A significant loss of named landrace varieties in both Europe and worldwide already caused a massive loss of crop genetic diversity and charged a substantial risk for future food security. The transfer of genetic diversity of European landraces into modern wheat cultivars can give valuable responses for climate change effects. The present study aims to introduce a high throughput state of the art genotyping system into the Hungarian breeding research to analyse the genetic diversity of the Central European landrace collection. The 15K wheat genotyping array uses 12.905 gene-based, predominantly haplotype-specific Single Nucleotide Polymorphism (SNP) markers providing a maximum of information accompanied by low analysis costs. We will use this genotyping system to identify favourable, new alleles of stress tolerance and quality in the Central European landraces. Comparisons to modern elite bread wheat cultivars will be presented and genome-wide association study will be carried out between SNPs and agronomically important traits. Phenotypic characterizations will be performed on 200 landraces and 70 modern wheat cultivars targeting ecological adaptation, biotic and abiotic stress tolerance and end-use quality. During this project we will identify new QTLs and genes, useful to improve limiting factors of grain yield, such as drought tolerance, plant phenology and resistance to diseases.