Synaptic plasticity is a fundamental property of neuronal and network functions, and it is considered to provide the biological bases of learning and memory. Using the whole-cell patch-clamp technique ex vivo, the research is focused on unravelling the mechanisms underlying plasticity in single neurons and their alterations in animal models of diseases (see the specific section). For example, we are currently working on the learning rules driving a form of spike-timing-dependent plasticity (STDP) in Golgi cells in the cerebellar cortex. This cell type represents the main source of inhibition in the cerebellar cortex input layer and is known to be a key determinant of cerebellar processing.
Besides plasticity, single neuron recordings are also applied to investigate the properties of single connections at different location of the cerebellar and cerebral cortex. In particular, this technique is ideal to characterize the integration of excitatory and inhibitory inputs on specific neurons and therefore to calculate the excitatory/inhibitory ratio at the single neuron level. The combination of patch-clamp with optogenetics is also used to determine neuronal input integration when dynamically changing the spatial distribution of such inputs.
A PhD student involved in this research topic will have the opportunity to learn the patch-clamp technique, which is the gold standard for investigating neuronal properties at the cellular and subcellular level with a precision level that is still unmatched by other techniques. The student will be involved in research projects characterizing the mechanisms of short- and long-term plasticity at synapses, the impact of the E/I balance on neuronal activity, the sub- and supra-threshold properties of different neuronal types in the cerebellar and cerebral cortex. Several research lines are also devoted to the characterization of the alterations of these properties in pathological models (see the dedicated section).
References
Pali E, D’Angelo E, Prestori F. Understanding Cerebellar Input Stage through Computational and Plasticity Rules. Biology (Basel). 2024 Jun 1;13(6):403. doi: 10.3390/biology13060403. PMID: 38927283; PMCID: PMC11200477.
Locatelli F, Soda T, Montagna I, Tritto S, Botta L, Prestori F, D’Angelo E. Calcium Channel-Dependent Induction of Long-Term Synaptic Plasticity at Excitatory Golgi Cell Synapses of Cerebellum. J Neurosci. 2021 Apr 14;41(15):3307-3319. doi: 10.1523/JNEUROSCI.3013-19.2020. Epub 2021 Jan 26. PMID: 33500277; PMCID: PMC8051689.
Sgritta M, Locatelli F, Soda T, Prestori F, D’Angelo EU. Hebbian Spike-Timing Dependent Plasticity at the Cerebellar Input Stage. J Neurosci. 2017 Mar 15;37(11):2809-2823. doi: 10.1523/JNEUROSCI.2079-16.2016. Epub 2017 Feb 10. PMID: 28188217; PMCID: PMC6596728