In vivo imaging of cortical organization and plasticity

 The cortex is a laminated structure that is thought to underlie sequential information processing. Sensory input enters layer 4 (L4) from which activity quickly spreads to superficial layers 2/3 (L2/3) and deep layers 5/6 (L5/6). Sensory responses themselves depend on ongoing, i.e. spontaneous cortical activity, as well as the state and behavioral context of the animal. Receptive field properties of neurons can rapidly and adaptively be reshaped when an animal is engaged in a behavioral task, indicating that even in primary auditory cortex encoding of stimuli is dependent on task- or context-dependent state (Francis et al 2018, Francis et al. 2022). Responses also depend on ongoing cortical dynamics in a lamina-dependent fashion. However, we do not know how neuronal circuits shape these emergent dynamics within and between laminae, and we do not know which neurons encode which aspect of a sensory stimulus. In a collaborative project (together with J. Maunsell, D. Rinberg, D. Plenz, M. Histed, S. Shoham, B. Babadi, T. Fellin, S. Panzeri, W. Losert, D. Chialvo; see HOLOBRAIN.ORG) funded by the NIH BRAIN initiative we use in vivo 2-photon imaging and stimulation technology that allows rapid imaging and stimulation in multiple focal planes and by developing new computational and analysis techniques based on dynamic systems and graph theoretic measures to extract network dynamics at the single neuron and population level. We use these new techniques to investigate the 3D single cell and population activity patterns in the auditory cortex in mice and identify  the influence of single neurons relative to the synergistic influence of specific groups of neurons (the crowd) on network dynamics and ultimately behavior of the animal. We already found that populations of neurons in A1 show neuronal avalanches (Bowen et al. 2019) and that they show a frctured columnar small world functional organization (Bowen et al. 2024).

Our work already identified the functional micro-architecture of the auditory cortex, and how this architecture can change and how change is influenced by top-down projections from the frontal cortex (see Bandyopadhyay et al Nature Neuroscience 2010, Winkowski & Kanold 2013, Winkowski et al. 2013, Meng et al. 2019, Liu et al. 2019, Mittelstadt & Kanold 2023).

In vitro studies of cortical micro-circuits

To understand how neurons are wired up we need to reveal their connections with each other. To do this we use in vitro single and 2-photon photostimulation, coupled with patch clamp recordings and 2-photon imaging. Photostimulation allows us to selectively stimulate neurons and we can then observe which other neurons are responding. Thus we essentially can create input and output connection maps of targeted neurons. By performing these studies across layers and across ages we aim to assemble a wiring diagram of the adult and developing brain. Our work already identified the micro-circuitry of L2/3 of auditory cortex (Watkins et al. 2014, Meng et al. 2017) and how it can change (Meng et al. 2015, 2017, 2019).

Effects of Developmental insults and Aging on sound processing

We are very interested in understanding how changes in cortical processing leads to changes in perception. Some changes in cortical processing and perception seem to happen quite “naturally”, e.g. when we age, and we are engaged in multiple studies unraveling what happens to sound encoding in old age.

While aging happens to all of us, developmental insults can also create life-long changes to the way the brain processes information. We thus also investigate the consequences of developmental manipulations or insults (e.g. perinatal drug exposure) in adult.