While the ex vivo approach is ideal to reconstruct subcellular, cellular, and network properties, how neurons operate in vivo needs to be investigated in the intact brain. This condition maintains the physiological connectivity within the brain and the physiological body functions active. To record neuronal activity in the intact brain, we use low-density MEA recordings in deeply anesthetized mice. The anesthetized condition allows to isolate and characterize specific connections (short-range and long-range) in the intact brain. For example, this allowed us to reconstruct complex properties of synaptic plasticity in the deep cerebellar nuclei, such as the impact of the theta-band oscillations on the direction of plasticity and the role of the cerebellar cortex to drive cerebellar nuclei activity. On the long-term range, we are currently applying this technique to study the indirect connectivity between the cerebellum and the prefrontal cortex, both in physiological conditions and in a mouse model of autism spectrum disorders. The cerebellar role in high-order cognitive function is now well established; however, a comprehensive understanding of how this is achieved is still lacking. We also combine optogenetics to selectively modulate the activity of specific neurons or connections.
A PhD student involved in this topic will have the possibility to investigate the complexity of brain connectivity and how different brain regions influence one another. The student will learn how to approach in vivo research, how to use electrophysiological tools to record neuronal firing in specific brain regions with stereotaxical coordinates, and how to apply optogenetic and electrical stimulation to characterize brain functional connectivity. This approach is particularly relevant to study how the alterations in neurons and small networks impact on the intact brain activity in vivo in pathological conditions (see the dedicated page).
References
Moscato L, Montagna I, De Propris L, Tritto S, Mapelli L, D’Angelo E. Long-Lasting Response Changes in Deep Cerebellar Nuclei in vivo Correlate With Low-Frequency Oscillations. Front Cell Neurosci. 2019 Mar 6;13:84. doi: 10.3389/fncel.2019.00084. Erratum in: Front Cell Neurosci. 2019 Jul 10;13:313. doi: 10.3389/fncel.2019.00313. PMID: 30894802; PMCID: PMC6414422.
Romano V, De Propris L, Bosman LW, Warnaar P, Ten Brinke MM, Lindeman S, Ju C, Velauthapillai A, Spanke JK, Middendorp Guerra E, Hoogland TM, Negrello M, D’Angelo E, De Zeeuw CI. Potentiation of cerebellar Purkinje cells facilitates whisker reflex adaptation through increased simple spike activity. Elife. 2018 Dec 18;7:e38852. doi: 10.7554/eLife.38852. PMID: 30561331; PMCID: PMC6326726.
Ramakrishnan KB, Voges K, De Propris L, De Zeeuw CI, D’Angelo E. Tactile Stimulation Evokes Long-Lasting Potentiation of Purkinje Cell Discharge In Vivo. Front Cell Neurosci. 2016 Feb 18;10:36. doi: 10.3389/fncel.2016.00036. PMID: 26924961; PMCID: PMC4757673.