Alteration of Neuronal Firing Properties afterIn VivoExperience in a FosGFP Transgenic Mouse

Abstract

Identifying the cells and circuits that underlie perception, behavior, and learning is a central goal of contemporary neuroscience. Although techniques such as lesion analysis, functional magnetic resonance imaging, 2-deoxyglucose studies, and induction of gene expression have been helpful in determining the brain areas responsible for particular functions, these methods are technically limited. Currently, there is no method that allows for the identification and electrophysiological characterization of individual neurons that are associated with a particular function in living tissue. We developed a strain of transgenic mice in which the expression of the green fluorescent protein (GFP) is controlled by the promoter of the activity-dependent gene c-fos. These mice enable an in vivo or ex vivo characterization of the cells and synapses that are activated by particular pharmacological and behavioral manipulations. Cortical and subcortical fosGFP expression could be induced in a regionally restricted manner after specific activation of neuronal ensembles. Using the fosGFP mice to identify discrete cortical areas, we found that neurons in sensory-spared areas rapidly regulate action potential threshold and spike frequency to decrease excitability. This method will enhance our ability to study the way neuronal networks are activated and changed by both experience and pharmacological manipulations. In addition, because activated neurons can be functionally characterized, this tool may enable the development of better pharmaceuticals that directly affect the neurons involved in disease states.

Arc Regulates Experience-Dependent Persistent Firing Patterns in Frontal Cortex

“…To measure intrinsic neuronal excitability, we used standard procedures to record resting potential, threshold for action potential, rheobase current, and input resistance for each neuron (Barth et al, 2004). To construct an input-output curve, we recorded frontal neurons in the current-clamp mode, and injected various amounts of current through the recording electrode to induce action potentials.…”

“…Experiments using the water maze task had earlier shown that deletion of the Arc gene in mice affects long-term memory consolidation, but not shortterm learning (Plath et al, 2006;Peebles et al, 2010). Using the accelerating rotarod task, we observed that, at the end of a 45 min motor-training session, all mice achieved similar rotation speeds before falling, regardless of genotypes (WT, with two complete copies of Arc; HET, with only one copy of Arc replaced by GFP; HOM, with both copies replaced by GFP; one-way ANOVA, F (2,55) ϭ 0.74, p ϭ 0.48; Figure 4A).…”

“…Our brain encodes information about past experience in specific populations of neurons that communicate with one another by firing action potentials (Silva et al, 2009;Barth and Poulet, 2012). Previous studies of experience-dependent plasticity have focused on how individual synapses respond to activity input (Luscher and Malenka, 2012).…”

“…When investigating this question in frontal cortical slices, the major challenge is distinguishing neurons activated by prior training experience from those unaffected by the experience in question. In this study, we focused on the activity-regulated cytoskeletonassociated protein (Arc/Arg3.1), which has been widely used as a marker for neurons activated by recent behavioral experience Barth, 2007). Although Arc has been implicated in experience-dependent changes of synaptic AMPAtype glutamate receptors (AMPARs) in hippocampal and visual systems (Bramham et al, 2008;Shepherd and Bear, 2011), its role in persistent firing has not been investigated.…”

Weak and Nondiscriminative Responses to Conspecifics in the Rat Hippocampus

“…6 E, rightmost panels; Table 4). The interpretation of this null result is ambiguous because there is no universal consensus regarding the meaning of c-Fos staining; it is at times considered a sign of previous action potential activity (Barth et al, 2004), and other times a trace of neuronal plasticity (Ito and Schuman, 2011). In the present context, these two interpretations lead to different predictions: if ventral hippocampus did, indeed, encode social stimuli, and if it did so by making some neurons fire less and some more, as observed in the neurons recorded in dorsal hippocampus, then the net effect of social interaction with novel individuals might be unaltered bulk activity, but the formation of new memories should lead to increased plasticity.…”