Enhanced metabolic capacity of the frontal cerebral cortex after Pavlovian conditioning

Abstract

While Pavlovian conditioning alters stimulus-evoked metabolic activity in the cerebral cortex, less is known about the effects of Pavlovian conditioning on neuronal metabolic capacity. Pavlovian conditioning may increase prefrontal cortical metabolic capacity, as suggested by evidence of changes in cortical synaptic strengths, and evidence for a shift in memory initially processed in subcortical regions to more distributed prefrontal cortical circuits. Quantitative cytochrome oxidase histochemistry was used to measure cumulative changes in brain metabolic capacity associated with both cued and contextual Pavlovian conditioning in rats. The cued conditioned group received tonefootshock pairings to elicit a conditioned freezing response to the tone conditioned stimulus, while the contextually conditioned group received pseudorandom tone-footshock pairings in an excitatory context. Untrained control group was handled daily, but did not receive any tone presentations or footshocks. The cued conditioned group had higher cytochrome oxidase activity in the infralimbic and anterior cingulate cortex, and lower cytochrome oxidase activity in dorsal hippocampus than the other two groups. A significant increase in cytochrome oxidase activity was found in anterior cortical areas (medial, dorsal and lateral frontal cortex; agranular insular cortex; lateral and medial orbital cortex and prelimbic cortex) in both conditioned groups, as compared to the untrained control group. In addition, no differences in cytochrome oxidase activity in the somatosensory regions and the amygdala were detected among all groups. The findings indicate that cued and contextual Pavlovian conditioning induces sustained increases in frontal cortical neuronal metabolic demand resulting in regional enhancement in the metabolic capacity of anterior cortical regions. Enhanced metabolic capacity of these anterior cortical areas after Pavlovian conditioning suggests that the frontal cortex may play a role in the retention and regulation of learned associations. KeywordsCytochrome oxidase; hippocampus; amygdala; context Cytochrome oxidase (CO) metabolic brain mapping provides an alternative approach for investigating neural circuits mediating Pavlovian conditioning, and it is a well-suited method for quantifying more stable neuronal metabolic capacity changes that reflect prolonged training (Poremba et al., 1997, Poremba et al., 1998b, Poremba et al., 1998a, Sakata et al., 2000, Villarreal et al., 2002, Conejo et al., 2005, Sakata et al., 2005. CO changes in the brain after prolonged training reach a more stabilized state of oxidative metabolism, and techniques which measure evoked brain metabolic activity, such as fluorodeoxyglucose (FDG) autoradiography, Corresponding author: F. Gonzalez-Lima, Dept. of Psychology, 1 University Station A8000, University of Texas at Austin, Austin, TX 78712-0187, Telephone: 512 471-5895, Fax: 512 471-4728, E-mail: Gonzalez-lima@mail.utexas.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that...

Involvement of the insular cortex in the consolidation and expression of contextual fear conditioning

“…Furthermore, an increase in cFos protein expression, a marker of neuronal activation, was observed in the IC induced by re-exposure to the aversively conditioned context, an effect attenuated by systemic treatment with diazepam, a standard anxiolytic drug, before the test session (Beck & Fibiger, 1995). In fact, fear conditioning studies commonly report IC activation in rodents and humans (Alvarez et al, 2008;Bruchey & Gonzalez-Lima, 2008). These data could explain our results showing that acute reversible inactivation of the IC before re-exposure to the aversive context (test session) attenuated the expression of conditioned emotional responses.…”

“…Interestingly, an increase in the activation of the IC has been observed after the re-exposure of rodents to an aversively conditioned context (Beck & Fibiger, 1995;Bruchey & Gonzalez-Lima, 2008), suggesting a possible involvement of this structure in the modulation of contextual fear conditioning. However, the precise role of the IC in fear conditioning is still not completely understood as studies investigating the effects of IC lesions have produced inconsistent results.…”

Chronic electrical stimulation of transected peripheral nerves preserves anatomy and function in the primary somatosensory cortex

“…We performed an optical density (OD) analysis of the neural activity by determining the intensity of the CyO staining through gray‐level measures following a previously described protocol (Bruchey & Gonzalez‐Lima, ). Selection of the sections was based on strict morphological criteria: (i) homogeneous CyO reaction for the two hemispheres; (ii) absence of histological artifacts in the PMBSF layers II/III and IV; and (iii) brain sections stained under the same conditions.…”

“…We tested our hypothesis by determining whether chronic electrical stimulation of an irreversibly transected sensory nerve [infraorbital nerve (IoN)] protects the SI from the long‐lasting negative effects inflicted by the transection. We combined histology and stereology with electrophysiological recordings to examine several prominent indicators: cortical somatosensory evoked potentials (EPs) for SI functionality; expression of cytochrome oxidase (CyO; a critical enzyme of the mitochondrial respiratory chain and a good marker of long‐term neuronal metabolic activity; Wong‐Riley, ; Bruchey & Gonzalez‐Lima, ) in order to assess the metabolic activity of the barrel cortex; volume of cortical layers to evaluate preservation of gross anatomical features; and number of PV‐ and Calb‐positive neurons (inhibitory GABAergic interneurons) in the SI to evaluate the electrical stimulation‐dependent cortical plasticity as most deafferentation‐related plasticity phenomena are mediated by disinhibition processes (Calford, ; Jiao et al ., ).…”

Structural preservation of deafferented cortex induced by electrical stimulation of a sensory peripheral nerve

“…CyO is the rate-limiting enzyme of the neural metabolism and, consequently, its expression level is directly related to the functional activity of the neurons [9]. Layer IV barrels in the somatosensory cortex (the morphological units corresponding to the vibrissae) are the most active regions due to their thalamocortical synapses [10].…”