, 2011). While

individual neurons can fire at high instantaneous frequencies, particularly in primary sensory cortices, the maximum sustainable average firing rate has been estimated to be between 1 and 4 Hz (Attwell and Laughlin, 2001). To achieve high instantaneous firing rates while maintaining low average firing rates, the cortex can optimize the fraction of neurons responding when the stimulus is presented (sparse population coding) and/or can optimize how frequently a single neuron responds when the stimulus is presented n times (lifetime sparseness, or Volasertib order fidelity as used hereafter) ( Willmore et al., 2011). Sparse coding optimizes the information per spike while minimizing mean firing rate and redundancy and, thus, minimizes metabolic load as a function of information ( Vinje and Gallant, 2000). Network models show that sparse internal representation facilitates the storage of learned associations, and cortical response sparsification may emerge as associations are learned (Chalupa and Werner, 2003). To examine the relationship between cortical sparsification and associative learning we carried out three sets of experiments. First, we developed a

variant of fear conditioning in Caspase inhibitor in vivo freely exploring mice in which whisker stimulation (our conditional stimulus [CS]) was either paired or explicitly unpaired with foot shock. Second, we examined how learning the association between the CS and the shock affected subsequent encoding of the CS

CYTH4 using in vivo calcium imaging. We measured population sparse coding, fidelity, and response strength. Third, to examine if our results were specific to associative learning, we measured the nonassociative effects of stimulus exposure on the population response. The primary somatosensory “barrel” cortex receives tactile information from the whiskers on the facial mystacial pad. This system has been exploited in restrained animals to study cortical plasticity induced by Pavlovian fear conditioning (Das et al., 2001, Galvez et al., 2006, Galvez et al., 2007 and Siucinska and Kossut, 1996), and in freely moving mice to induce associative eye blink conditioning (Galvez et al., 2009). For our studies, we first determined whether freely exploring mice learn Pavlovian fear conditioning where whisker stimulation is used as a CS. Passive whisker stimulation in freely behaving mice was accomplished by gluing a small metal grain to a specific whisker and placing the mouse in the bore of an electromagnet (7.7 mT) large enough to permit free exploration (Melzer et al., 1985) (Figure 1A). In mice conditioned to associate whisker stimulation with shock, 30 s of whisker stimulation at 8 Hz immediately preceded a single 0.6 mA, 1.5 s foot shock (paired group); this pairing was repeated five times, with a mean interval of 3 min between pairings, in a single day (Figure 1B top).