Thesis supervisor: Attila Gulyás
Location of studies (in Hungarian): Semmelweis Egyetem Abbreviation of location of studies: SE
Description of the research topic:
Semmelweis University – János Szentágothai Doctoral School of Neurosciences
The hippocampus plays a pivotal role in learning and memory consolidation. An important aspect of learning processes is that hippocampal activity is accompanied by two, behavior associated EEG patterns: the theta and the sharp-wave ripple (SWR) activity. In both cases, the EEG signals show specific background oscillatory frequency components (40 and 200 Hz), which enables the synchronous activity of the neurons. These activity patterns are correlating with the animal’s behavior, and it is governed by the dynamic balance of excitation and inhibition. The result of enhanced excitation or inhibition can lead to the deterioration of balanced activity, resulting in pathological activity patterns, e. g.: epilepsy. The highly diverse hippocampal inhibitory neurons (IN) play an important role in governing the spike timing of neurons, and granting the proper excitatory-inhibitory balance during the discussed oscillations.
Hippocampal activity patterns correlating with behavior are modulated by the medial septum. The medial septum creates reciprocal connections with the hippocampus, and INs are also involved in this circuitry: the septo-hippocampal GABAergic pathway selectively innervates hippocampal INs, and an IN population projects back to the medial septum.
A variety of functionally different IN groups were identified so far with different anatomical, pharmacological and physiological properties. How an IN effects the activity of other neurons is mainly determined by what subcellular compartments are targeted by its synapses. Based on this property, we can distinguish between perisomatic or dendritic targeting INs, or IN-selective INs.
Our previous investigations revealed how the synaptic connections are organized among IN subtypes. Big differences were found between the organization and distribution of synaptic inputs and outputs of parvalbumin (PV), calbindin (CB), calretinin (CR) and cholecystokinin (CCK) containing INs, furthermore, the balance between excitatory and inhibitory inputs are also diverse. These results suggest, that IN subtypes are activated by different hippocampal inputs, and at different activity levels.
Our lab revealed two distinct types of hippocampal basket cells (BCs), a PV containing, and a CCK/VIP containing group. The distinction is important, since the two groups show different properties. PV cells contain 2-type muscarinic receptors, while CCK cells contain CB1 receptors at their axon terminals. Furthermore, CCK cells receive inputs from the raphe nuclei and contain 5HT3 receptors, while these inputs avoid CCK cells. This two subtypes of BCs are therefore modulated differently, therefore, it is likely that they have distinct functions in governing the activity of the hippocampus.
In the near future, we want to address the following questions:
1) We want to reveal how the different IN subtypes are integrating their inputs, by using electrophysiological recordings combined with high definition, temporally and spatially patterned optogenetic stimulation?
2) How the integrative properties of IN subtypes are changing by the presence of subcortical modulatory transmitters, e. g.: due to elevated cholinergic tone?
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