Robert P. Machold, PhD

My research is focused on understanding how the brain gathers and interprets information from the outside world.  Conscious perception of events in our daily lives requires that the sensations we receive from our surroundings are placed into the context of our previous experiences. The integration of sensory ("bottom-up") information with our internally-generated ("top-down") expectations takes place in the neocortex, a multi-layered structure that makes up the majority of the brain in mammals from rodents to humans. The circuitry of the neocortex is comprised of two primary cell types: glutamatergic pyramidal neurons (~85%) that send excitatory signals to other neurons throughout the brain, and GABAergic interneurons (~15%) that provide local inhibition of cortical activity. Imbalances in excitatory and inhibitory activities in the brain are thought to be central to a diverse range of neurocognitive disorders, including autism spectrum and schizophrenia.   

In collaboration with a number of laboratories here at the NYU Grossman School of Medicine, particularly the lab of Bernardo Rudy of which I am a member, as well as external labs (e.g., the lab of Gord Fishell at Harvard Medical School), I have pursued a variety of research questions on how different subtypes of GABAergic interneurons are specialized to provide distinct forms of inhibition, as well as how neuromodulators such as acetylcholine alter cortical circuit activity during learning and attention. To accomplish these research goals, I have integrated recent single cell transcriptomic profiling data (e.g., from the Allen Institute) with intersectional genetic approaches in mice to target specific neuronal populations for circuit-level and behavioral studies. 

At present, with the Rudy lab, I am studying how GABAergic interneurons within superficial cortical layers regulate the flow of top-down information to enable context-based learning. These interneuron species include VIP-expressing subtypes mostly located in layers 2 and 3, as well as NDNF-expressing subtypes that are specialized for layer 1, the most superficial layer of the neocortex where a variety of long-range signals from distant cortical and thalamic regions converge on the apical tuft dendrites of pyramidal neurons. Collectively, these VIP and NDNF interneurons play a critical role in enabling the integration of top-down and bottom-up information during animal behavior. I also work with several other research teams here within the Neuroscience Institute at the NYU Grossman School of Medicine to elucidate the mechanism by which neuromodulators such as acetylcholine and oxytocin alter neural circuit activity to enable behavioral adaptation and flexibility.