1. A synaptic memory trace for cortical receptive field plasticity Robert Froemke, Michael Merzenich & Christoph Schreiner Andrew Lysaght HST.723 April 22, 2009

2. Background Previously known: Receptive fields of cortical neurons are plastic o Fritz et al. showed this begins very rapidly Nucleus basalis (NB) is critical o Projects widely o Cholinergic Question: What is the mechanism of synaptic plasticity?

3. Experiment 1 Adult rat A1: Whole-cell recording (VC mode) Monitored EPSCs/IPSCs Pure-tone stimulus (contra) Paired excitation of NB

4. Observations Before pairing: High correlation between excitation and inhibition After pairing: Potentiated EPSCs Depressed IPSCs Changes localized to tone frequency

5. Observations Main effect is to break balance of excitation and inhibition (required paired stimulation)

6. Impacts on firing Increased probability of firing Increased probability of multiple spikes Net effect: increased cortical response to stimulus

7. Onset time course Inhibition ≈ 20 s Excitation ≈ 60 s Effect is cholinergic NB provides spectro-temporally restricted dis-inhibition Allows for Hebbian synaptic plasticity

8. Offset time course Increased excitation persists Inhibition slowly matches excitation (≈ 2 hours) Inhibition recovery requires repeat stimulation

9. Experiment 2 Question: Where does this modulation occur? Applied stimulation at two cortical inputs: Ventral Medial Geniculate Body (Thalmus) Primary Auditory Cortex Observed which input was altered by pairing

10. Location of alteration Inputs from thalamus are unaffected Connections to original BF region of A1 strengthened

11. Conclusions NB stimulation increased preference for stimulus o Inhibition suppressed rapidly o Excitation potentiated o Inhibition slowly recovers o Alteration derived from cortical inputs Possible mechanism for attention-based modulation Allows transient increase in response to stimuli deemed important (before receptive fields have time to adapt)

12. Questions Missed inputs? Is this behavior normal? o Inter-neurons are most affected by anesthesia o Synaptic response to electrical vs. acoustic stimulation