Abstract:
Repeated experience with a sensory stimulus can cause perceptual learning, with
cerebral cortical responses changing as behavioral improvement occurs. However, since
sensory stimuli change the activity of neurons in many different areas of the brain, it has
been unclear whether learning creates changes in the cortex, or whether changes in cortical
activity reflect changes in afferent input. Here, to determine whether learning-related
changes happen directly in local cortical circuits or if all changes occur in downstream
areas, we take advantage of the fact animals can learn to base their behavior on non-natural
(“off-manifold”) activity patterns evoked by direct stimulation, which allows us to reliably
induce stimulation in the same cortical neurons on repeated trials, bypassing afferent areas.
We trained mice to detect and report the presence of neural activity evoked by optogenetic
stimulation (ChrimsonR in excitatory neurons of primary visual cortex, V1), and found
large behavioral improvements as animals learned to detect this stimulus. Animals were
first trained to detect a visual stimulus of varying contrast. An optogenetic stimulus was
then paired with every visual stimulus. When performance increased for the lowest contrast
visual stimulus, the visual stimulus was turned off and animals performed the task based
on the optogenetic stimulus alone. As animals gained experience with the optogenetic
stimulus presented alone, animals’ reaction time decreased (-15.9±3.8 ms, per training
session, median±SEM, p<0.01, N=9 mice), and detection performance to the stimulus
intensity improved (by over an order of magnitude). We imaged calcium responses in local
V1 neurons before and after learning (before the optogenetic stimulus is presented and after
animals’ detection performance for the optogenetic stimulus improved) and found changes
in local cortical activity. Visual selectivity for direction and orientation was decreased by
optogenetic learning, but overall neural responses became larger. These data suggest local
cortical circuitry does adapt to support learning and that cortical processing of one type of
stimulus (an ‘on-manifold’ visual stimulus) is degraded by learning another type of
stimulus (an “off-manifold” optogenetic stimulus), while neural responses can be
enhanced.
