For decades, it has been postulated that information is represented in the brain by patterned neuronal activations. Single neurons do not act as isolated computational units: rather, neurons act together in a complex circuit, to relay, process and store information. Furthermore, it has been postulated that repeating patterns of neuronal activity are instantiations of recent memory consolidation.
UP states, periods of prolonged depolarization, identify functional networks of interconnected neurons in local patches of neocortex. Recently, I have demonstrated that UP states are synonymous with patterned and stereotyped sequences of neuronal activity. I propose to investigate the role of stereotyped sequences in synaptic plasticity within these identified neocortical networks. My working hypothesis is that patterned circuit activity encodes recent input to the circuit. The pattern can be stored in the circuit and later recalled, as indicated by its replay. The hypothesis predicts that patterns of activity, which arise during UP states, are reinforced by synaptic plasticity mechanisms, becoming increasingly stereotypic or ‘hard wired’. Thus these replayed patterns may serve to consolidate the transient effects of circuit inputs into long-lasting circuit modifications.
To test this hypothesis I will evaluate whether circuit dynamics facilitate synaptic plasticity in a network and further whether this plasticity promotes the addition of neurons to the circuit. Both may be important mechanisms by which information is stored within neocortical circuits. Finally I will evaluate whether the circuit dynamics changes the rules that govern the plasticity of individual synapses. Characterization of neuronal plasticity at the circuit level during naturalistic circuit activity is a crucial step in understanding the neural basis for learning and memory.
These novel datasets will reveal fundamental and mechanistic insights into how memory is stored and information is processed at the circuit level. Cognitive and memory deficits are common to many neurological disorders and current treatment attempts to fix a problem that we do not understand. Thus, revealing the fundamental mechanisms underlying these processes will better inform potential targets for therapeutic intervention.