Mapping Activity in the Auditory Pathway with C-Fos

Abstract

Induction of the immediate-early-gene c-fos occurs in response to a wide variety of external stimuli, and therefore represents a method to functionally map neuronal activity in the brain with cellular resolution. We investigated systematically in rats the distribution of Foslike activity in the auditory pathway elicited by various types of stimulation of the cochlea.

In response to pure tones (45 minutes exposure), Fos-like immunoreactivity (FLI) was found to form bands reflecting the tonotopic arrangement of neurons in the dorsal (DCN) and posteroventral (PVCN) cochlear nuclei, the lateral superior olive (LSO), the dorsal nucleus of the lateral lemniscus (DLL) and the central nucleus of the inferior colliculus (CIC). Surprisingly, virtually no FLI was observed in the anteroventral cochlear nucleus (AVCN) and the ventral division of the MGB (vMGB). In the primary auditory cortex (Te 1), FLI was present but did not reveal its tonotopic organization.

After electrical stimulation of the whole cochlea, FLI was found to cover the entire extent of DCN, PVCN, LSO, DLL as well as non-tonotopic nuclei such as the external (ECIC) and dorsal (DCIC) nuclei of the inferior colliculus, the medial (mMGB)and dorsal (dMGB) divisions of the medial geniculate body. FLI was also broadly and unspecifically distributed in the 3 auditory cortical areas Te 1, Te2 and Te3. In contrast, no FLI was seen in AVCN, CIC and vMGB. Even a short period of stimulation (5 minutes) was sufficient to significantly increase FLI in most of the above auditory nuclei. Changing the intensity or duration of stimulation and the survival time could modify substantially the distribution of FLI. Similarly, using another commercial source of antibody against c-los could make FLI to be detected in AVCN and the CIC, but not in vMGB.

FLI was established in the auditory pathway of rats during the successive steps of the learning of a complex sensorimotor task. At all steps of learning, FLI was constant in the subcortical auditory nuclei, namely in DCN, the posteroventral cochlear nucleus (PVCN), LSO, the dorsal nucleus of the lateral lemniscus (DLL), CIC, ECIC, DCIC, mMGB and dMGB. As observed above for passive listening, no or little FLI was observed in AVCN and vMGB. In contrast to the subcortical auditory nuclei, a differential FLI distribution reflecting the progessive steps of task learning was found in the auditory cortical areas.

Taken together, these data indicate that c-fos is not a general functional marker of activity. C-fos is characterized by a significant degree of selectivity for certain stimuli; in addition, for the same stimulus, c-fos expression depends on the context. Furthermore, FLI appeared to be induced preferentially in some cell types (small neurons) as opposed to others (large neurons). Parameters of stimulation (duration, intensity, survival time) and the age of the animal play also an important role, as well as the type of antibody used to visualize Fos activity.