The human brain is a tremendously complex neuronal circuit that we don’t really understand. For example we do not know how sensory information about the world is encoded in neuronal population activity and transformed into a percept.

    We thus investigate how information his encoded in the brain (the “neural code”) and how this code is read out to make behavioral decisions and cause percepts. It is clear now that we do not come hard-wired but that interaction with the environment plays a major role in shaping our brain. In particular during early life sensory experience shapes the refinement of connections in the brain but after the critical period only limited remodeling (plasticity) is possible. The period during which sensory experience elicits its powerful influence starts in the womb since babies are born with a preference for their mother’s voice. Thus, since the encoding of sensory information in the brain depends on experience we are also very interested in uncovering how experience shapes neuronal circuits and encoding of stimuli.

    The fact that only limited plasticity is present after the critical period is a serious problem because it means that one has to diagnose and correct problems early in infancy for normal development to occur. Of course we all know that we can learn some thing later in life thus we might be able utilize or enhance adult plasticity to reverse developmental abnormalities. We thus also investigate what happens to the brain when we learn new things..

    Thus, we are identifying specific circuits in the brain, trying to understand how they work, how they encode information about the world,  and how they can change, and how they come to be. To do this we build, we code, we experiment, and we ponder.

Our work is supported by NIDCD , NEIAFOSR, and the BRAIN initiative.

Current Projects

Neuronal Circuits in Early Development

Sensory experience even early in life can shape our brains. For example newborns can recognize their mother’s voice. How does this early experience sculpt the brain? What circuits does experience act on? Thus one focus of our research is aimed at figuring out what circuits and mechanisms allow the cortex to develop and be plastic in early life. We previously identified a specific group of neurons present predominantly in the developing brain, subplate neurons, that play a key role in this process (see Kanold & Luhmann 2010, Molnar, Luhmann, Kanold 2020). These neurons are the first to receive inputs from the thalamus and project into the (future) thalamorecipient layer 4. Loss of subplate neurons prevents cortical development. Current work in the lab is investigating how these neurons control cortical development, how they are integrated in the developing cortical circuitry (see Zhao et al. 2009, Viswanathan et al 2012, Tolner et al 2012, Meng et al. 2014, Viswanathan et al. 2016, Deng et al. 2017), how their function is disrupted in neurodevelopment disorders such as autism (Nagode et al. 2017). We recently showed that subplate circuits are sculpted by early sensory experience (Meng et al. in 2021, Mukherjee et al. 2021) making them the earliest cortical substrate of experience dependent changes. Subplate neurons also share many similarities with the claustrum (Molnar, Luhmann, Kanold 2020) and we are thus interested in the global role of subplate during development.

More information here.

Cortical information processing 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 sensory cortices 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 large-scale collaborative project (together with J. Maunsell, D. Rinberg, D. Plenz, M. Histed, S. Shoham, B. Babadi, T. Fellin, S. Panzeri, W. Losert, D. Chialvo) 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 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.

    Our work already identified the micro-circuitry of L2/3 of auditory cortex (Watkins et al. 2014, Meng et al. 2017), the functional micro-architecture of the auditory cortex, and how this architecture can changes (see Bandyopadhyay et al Nature Neuroscience 2010, Winkowski & Kanold 2013, Winkowski et al. 2013, Winkowski et al. 2018, Kanold et al. 2014).

More information here.

Crossmodal plasticity of sensory cortical processing

Sensory systems do not work in isolation. Moreover, it is well known that visual deprivation (such as blindness) can lead to improved auditory abilities. However the underlying mechanisms that contribute to these “supernormal” abilities are largely unknown. We are interested in investigating what happens to other cortical areas in particular the auditory cortex when visual experience is altered for short time periods. Our results so far show that brief visual deprivations (simulated blindness) alter auditory processing and thalamocortical synapses  (Petrus et al Neuron 2014) and intracortical connection in the auditory cortex (Meng et al. 2017, Meng et al. 2015, Petrus et al. 2015). Thus some of the changes seen in auditory performance are likely due to changes in the auditory cortex. Moreover seeing changes in thalamocortical connections to auditory cortex is quite surprising as our visual deprivations occur after the critical period and indicate that crossmodal influence seem to be more powerful than unimodal influences in changing cortical circuits. . More details here

Age related changes and dysfunctions in auditory 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. It is well known that our ability to hear sounds and understand speech decreases as we age. This defecit is especcially acute when listening under challenging conditions, e.g. in noisy restaurants or bars. Indeed, age-related hearing loss (presbycusis) affects one-third of the world’s population and one hallmark of presbycusis is difficulty hearing in noisy environments. While much focus has been placed on age-related changes to the inner ear, less is known about the age-related changes in the brain that affect auditory processesing. We embarked on rvealing how age changes the processing of sound information in the auditory cortex and what the underlying ciruit changes are with the goal to prevent or reverse these changes. So far our work in mice has shown that auditory cortex contains distinct subpopulations of excitatory neurons that aging increases correlated activity between neurons and thereby reduces the response diversity in auditory cortex and leads to defecits in sound encoding (Shilling-Scrivo et al. 2021). Imaging in mice trained to detect tones in noise we found that aging reduces the ability to suppress its responses to background noise. This excess activity additionally leads to increased correlations between neurons, reducing the amount of relevant stimulus information in the auditory cortex (Shilling-Scrivo et al. 2022, JHU news). We are now investigating the underlying circuit changes.

More information here