Data Blitz Talks
Juliet Bottorff
(Turrigiano Lab)
Behavioral State Control of Neuroplasticity
At Brandeis, researchers are not only making advances in brain science, but also in the creation of new research tools. Ms. Bottorff discussed her work examining neuronal activity in the vision center of rat brains following sight deprivation in one eye. She has made use of a fluorescent protein, called Campari, to duplicate results found in brain recordings of freely moving rats. This opens the door to using this method in other behavior and learning studies.
It’s clear that sleep and wake states have a profound influence on cortical plasticity and they are necessary for many forms of functional learning and memory. They also represent distinct brain states, during which neuromodulation and activity patterns are dramatically different. Given that neuromodulators are strong regulators of plasticity and cortical activity patterns, this suggests that sleep or wake, via specific neuromodulators, may select for distinct plasticity mechanisms. Many studies have investigated the roles of sleep and wake states in the efficacy of different plasticity mechanisms, but results have lacked any explanation for how state-specific plasticity selection may occur. Our lab has studied this fundamental question using behavioral tracking and continuous extracellular recordings from visual cortex (V1) of freely behaving rats throughout the well-established monocular deprivation (MD) paradigm. This paradigm induces a suppression of V1 firing rates followed by a rebound back to baseline, termed firing rate homeostasis (FRH). Thus, our lab showed that FRH occurs exclusively during active wake (AW) behavioral states. One of the biggest differences in the brain during AW is the level of cholinergic input from the basal forebrain (BF). Basal forebrain cholinergic neurons contribute strongly to AW specific cortical activity patterns and are key regulators of multiple forms of learning and plasticity. Using the same in vivo extracellular recordings described above, I have preliminary data to suggest that inhibition of these neurons after MD makes V1 activity patterns more sleep-like and prevents FRH from occurring. Furthermore, I have begun using Campari, an activity-dependent photoconvertible fluorescent protein, as a higher-throughput tool with which to measure population level activity of V1 neurons after MD. Along with essential validating work by a postdoc in our lab (Nick Trojanowski), I have shown that this method is capable of capturing neuronal activity dynamics known to occur in vivo, including the drop and rebound of V1 neuron activity after MD, and that inhibiting BF cholinergic neurons prevents the rebound of this activity. These results suggest that neuromodulators, and specifically acetylcholine, may indeed play a crucial ‘gatekeeper’ role in the induction of plasticity, specifically FRH. Moreover, they suggest that Campari is a valuable tool with which to further dissect cellular and molecular mechanisms regulating firing rate homeostasis. This opens the door for many exciting future directions that will help illuminate how behavioral states can selectively coordinate distinct plasticity mechanisms in vivo.