Our interactions with the outside world trigger changes that are critical for proper brain development and higher cognitive function. The Greenberg laboratory has a long-standing interest in the ways in which experience-driven neural activity shapes the developing and mature mammalian nervous system. In the mid-1980s, our lab discovered that growth factors and neurotransmitters trigger the rapid transcription of the Fos gene. Ever since, we have focused on elucidating the nature and role of neuronal transcriptional programs triggered by extracellular stimuli. There are strong links between these processes and various human conditions that involve cognitive dysfunction, such as autism spectrum disorder. We continually seek to exploit molecular insights to advance not only the understanding of brain development and plasticity, but also the etiology and treatment of clinically relevant neurological conditions.

Sensory experience influences neural circuit assembly and refinement. In part, it does so by driving the expression of specialized cohorts of genes in neurons of the developing brain. These important activity-dependent gene programs are highly cell type- and brain region-specific and have thus been challenging to study in vivo. To overcome these challenges, we have begun characterizing the effects of gene programs within the context of specific neural circuits using a combination of techniques, such as molecular genetics, high-throughput sequencing, and electrophysiology. Our efforts aim to understand how neuronal subtypes are differentially regulated by experience. We are also investigating the contribution of the distal genetic elements and the cognate genes that such subtypes control to nervous system development and function. A long-term goal is to understand how activity-dependent regulatory sequences and protein coding-genes shape transcriptional outputs and modulate neuronal activity-dependent phenotypes. We are particularly interested in exploring excitatory and inhibitory synapse formation and maturation, the process of synapse elimination, and the neuronal plasticity that underlies learning memory and behavior.

Much of our work is conducted in the rodent; however, we are increasingly aware of the need for non-rodent model systems to achieve a full understanding of human brain development and disease. To begin to address human-specific aspects of neuronal activity-dependent signaling, we are also exploring the activity-dependent epigenetic, transcriptional, and post-transcriptional responses of human, macaque, and marmoset neurons.