Rethinking things past: Both Hebbian plasticity and neuromodulation essential to memory formation
PostedDecember 31, 2014
Auditory CS-evoked responding in LA cells, preferential ArchT expression in LA pyramidal neurons, and optical inhibition of aversive shock-evoked responding. (A) Population-averaged auditory-evoked field potential response amplitude (y axis) in response to the final auditory CS pip (the time point at which the auditory stimulus will overlap with the aversive shock during subsequent training) before threat conditioning. The x axis “0” point represents the onset of the auditory stimulus. Red arrows denote the short latency portion of the response, which is known to be potentiated following fear conditioning and was used for the statistical analyses as in prior work. (B) Population-averaged CS-evoked firing rate responses during the preconditioning test session from single tone-responsive LA neurons (n = 11/38 total cells) recorded in awake, behaving animals (−5 − 25 s total time period in PSTH from CS onset at first gray bar, 250-ms bins on x axis). Gray bars under the x axis denote individual auditory pips during the CS with the final pip denoted by a red bar. (C) ArchT (Left) and CaMKIIα (Center), a marker for LA pyramidal neurons, immunolabeling in LA sections. Overlayed image is shown on Right. (D, Left) Graphical depiction of dual optogenetic illumination and LA neural recording of shock-evoked responses. (Right) Population-averaged peri-event time histogram showing footshock-evoked firing rate responses (in spikes per second) in extracellularly recorded LA neurons (n = 7) without (red trace) or with (green trace) overlapping laser illumination. Shock-evoked responses were significantly larger during the shock alone compared with shock + laser trials (Wilcoxon matched-pairs test: Z = 2.20, P = 0.03). Credit: Johansen JP, et al. (2014) Hebbian and neuromodulatory mechanisms interact to trigger associative memory formation. Proc Natl Acad Sci USA 111(51):E5584-E5592.
In 1949, Donald O. Hebb (often called the father of neuropsychology and neural networks) published The Organization of Behavior: A Neuropsychological Theory1, connecting the two previously distinct areas of higher cognitive brain function and neural biology. His theory, known as Hebbian learning – and which came to be known as the Hebbian plasticity hypothesis – posited that “when an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A‘s efficiency, as one of the cells firing B, is increased.” (While often described in lay terms as cells that fire together, wire together, this omits the necessary causality involved: Hebbian learning requires that cell A fires just before, not coincident with, cell B – an important factor that presaged spike-timing-dependent plasticity, which adjusts the strength of connections between neurons in the brain based on the relative timing of a particular neuron’s output and input action potentials, the latter referred to as spikes.)