Arc Regulates Experience-Dependent Persistent Firing Patterns in Frontal Cortex

Abstract

The brain encodes information about past experience in specific populations of neurons that communicate with one another by firing action potentials. Studies of experience-dependent neural plasticity have largely focused on individual synaptic changes in response to neuronal input. Indicative of the neuronal output transmitted to downstream neurons, persistent firing patterns are affected by prior experience in selective neuronal populations. However, little is known about the molecular and cellular mechanisms by which experience-related persistent firing patterns are regulated in specific neuronal populations. Using frontal cortical slices prepared from transgenic mice carrying a fluorescent reporter of Arc gene expression, this study investigates how behavioral experience and the activity-regulated Arc gene affect patterns of neuronal firing. We found that motor training increases Arc expression in subsets of excitatory neurons. Those neurons exhibit persistent firing in contrast to Arc-negative neurons from the same mice or neurons from the untrained mice. Furthermore, in mice carrying genetic deletion of Arc, the frontal cortical circuitry is still in place to initiate experiencedependent gene expression, but the level of persistent firing thereafter is diminished. Finally, our results showed that the emergence of persistent activity is associated with Arc-dependent changes in the function of NMDA-type glutamate receptors, rather than changes in AMPA-type receptors or membrane excitability. Our findings therefore reveal an Arc-dependent molecular pathway by which geneexperience interaction regulates the emergence of persistent firing patterns in specific neuronal populations.

Visual experience sculpts whole-cortex spontaneous infraslow activity patterns through an Arc-dependent mechanism

“…4D), which showed increased visual homotopic correlation and increased visual-anterior area anticorrelation. One statistically significant PC was also found in the WT-NV vs. WT-MD correlation difference ( mice have normal lateral geniculate nucleus anatomy and visual cortex retinotopy (42), and cortical neuron membrane excitability is not altered (43). Additionally, Arc −/− mice have precritical period visual-evoked potentials that are identical to those found in WT (42).…”

“…Importantly, prior studies have shown that Arc gene deletion does not alter growth curves, visual system anatomy, visual cortex retinotopic maps, visual-evoked potentials, or cortical neuron membrane excitability (42)(43)(44). Thus, the experience-dependent processes that were attenuated in Arc −/− mice are not attributable to disrupted basic visual functionality, but to specific action of Arc on experience-driven synaptic change.…”

Disruption of hippocampal–prefrontal cortex activity by dopamine D2R-dependent LTD of NMDAR transmission

“…We demonstrate that the normal EPSP summation and spike firing in layer 5 pyramidal neurons, driven by bursts of activity in hippocampal afferents, is significantly attenuated after activity-dependent LTD of NMDAR transmission. Previous studies have underlined the importance of NMDAR transmission in temporal summation between pairs of PFC pyramidal neurons, where they may play a key role in recurrent excitation (48) and persistent firing (49). Such effects may contribute to working memory processes in PFC.…”

Motor Learning Consolidates Arc-Expressing Neuronal Ensembles in Secondary Motor Cortex

“…Arc expression is induced by motor learning in motor cortical neurons (Hosp et al, 2013; Ren et al, 2014), and application of protein synthesis inhibitors to motor cortex (Dayan and Cohen, 2011; Kleim et al, 2003; Luft et al, 2004) or genetic knockout of Arc (Ren et al, 2014) disrupts long-term motor learning behavior. However, the cellular process by which Arc is involved in motor learning remains unknown.…”

“…This task robustly activates neurons in motor cortical areas and increases the level of Arc expression (Costa et al., 2004; Ren et al, 2014). Therefore, this rotarod training task is well suited for the study of neuronal recruitment and consolidation in motor learning.…”