Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Synaptic Plasticity and Hebbian Cell Assemblies

Gerkin, Richard Christopher (2008) Synaptic Plasticity and Hebbian Cell Assemblies. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

Primary Text

Download (4MB) | Preview


Synaptic dynamics are critical to the function of neuronal circuits on multiple timescales. In the first part of this dissertation, I tested the roles of action potential timing and NMDA receptor composition in long-term modifications to synaptic efficacy. In a computational model I showed that the dynamics of the postsynaptic [Ca2+] time course can be used to map the timing of pre- and postsynaptic action potentials onto experimentally observed changes in synaptic strength. Using dual patch-clamp recordings from cultured hippocampal neurons, I found that NMDAR subtypes can map combinations of pre- and postsynaptic action potentials onto either long-term potentiation (LTP) or depression (LTD). LTP and LTD could even be evoked by the same stimuli, and in such cases the plasticity outcome was determined by the availability of NMDAR subtypes. The expression of LTD was increasingly presynaptic as synaptic connections became more developed. Finally, I found that spike-timing-dependent potentiability is history-dependent, with a non-linear relationship to the number of pre- and postsynaptic action potentials. After LTP induction, subsequent potentiability recovered on a timescale of minutes, and was dependent on the duration of the previous induction. While activity-dependent plasticity is putatively involved in circuit development, I found that it was not required to produce small networks capable of exhibiting rhythmic persistent activity patterns called reverberations. However, positive synaptic scaling produced by network inactivity yielded increased quantal synaptic amplitudes, connectivity, and potentiability, all favoring reverberation. These data suggest that chronic inactivity upregulates synaptic efficacy by both quantal amplification and by the addition of silent synapses, the latter of which are rapidly activated by reverberation. Reverberation in previously inactivated networks also resulted in activity-dependent outbreaks of spontaneous network activity. Applying a model of short-term synaptic dynamics to the network level, I argue that these experimental observations can be explained by the interaction between presynaptic calcium dynamics and short-term synaptic depression on multiple timescales. Together, the experiments and modeling indicate that ongoing activity, synaptic scaling and metaplasticity are required to endow networks with a level of synaptic connectivity and potentiability that supports stimulus-evoked persistent activity patterns but avoids spontaneous activity.


Social Networking:
Share |


Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Gerkin, Richard Christopherrig4@pitt.eduRIG4
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairSimons, Daniel Jcortex@pitt.eduCORTEX
Committee MemberBarth, Alison
Committee MemberSchwartz, Andrew Babs21@pitt.eduABS21
Committee MemberBi, Guo-Qianggqbi@pitt.eduGQBI
Committee MemberRubin, Jonathan Erubin@math.pitt.eduJONRUBIN
Committee MemberStaley, Kevin
Committee MemberKass, Robert
Date: 18 April 2008
Date Type: Completion
Defense Date: 15 January 2008
Approval Date: 18 April 2008
Submission Date: 17 April 2008
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Neurobiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: asynchronous; calcium; computation; Hebb; homeostasis; LTD; LTP; model; plasticity; reverberation; scaling; STDP; synapse
Other ID:, etd-04172008-151338
Date Deposited: 10 Nov 2011 19:38
Last Modified: 15 Nov 2016 13:40


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item