Neurobehavioral consequences of cortical adaptation disruption during ontogeny

Abstract

Filtering of redundant or stable inputs is a critical function of all sensory pathways. Normal sensory gating can allow processing resources to be differentially devoted to changing or otherwise biologically significant stimuli. In olfaction, short-term odor habituation is mediated by a metabotropic glutamate receptor (mGluR)-mediated depression of afferent synapses in the piriform cortex. Given the role of early experience in shaping cortical function and anatomy, the present experiments examined the effects of chronic habituation disruption during development on behavior and local circuit anatomy. Rats were chronically intracerebrally infused with the mGluR group III antagonist (RS)-a-cyclopropyl-4-phosphonophenylglycine (CPPG) during early development. The results demonstrated that early onset mGluRIII blockade resulted in a long-lasting decrement in odor habituation compared to controls, evident for at least 2 weeks post-infusion offset. Odor investigation time in the youngest animals was correlated with cortical laminar thickness, though the long-lasting behavioral effect showed no such correlation. No changes in apical dendritic spine density in the piriform cortex were detected. Combined with previous work, these results suggest that sensory gating disruption during development can have both immediate and long-lasting effects on sensory guided behavior.

Cortical Processing of Odor Objects

“…This cortical adaptation is mediated by pre-synaptic metabotropic receptors (group III) which reduce glutamate release from mitral/tufted cell axons during repetitive stimulation (Best and Wilson, 2004). Pharmacological blockade of mGluRIII receptors within the piriform cortex prevents afferent synaptic depression, cortical odor adaptation, and short-term behavioral habituation (Bell et al, 2008; Best et al, 2005; Yadon and Wilson, 2005). Noradrenergic inputs to piriform cortex can also reduce synaptic depression (Best and Wilson, 2004), potentially via pre-synaptic beta receptors on mitral cell axons.…”

Epigenetics and Biomarkers in the Staging of Neuropsychiatric Disorders

“…Keuroghlian and Knudsen (2007) have reviewed experimental evidence showing experience-dependent plasticity in the central auditory representations of sound frequency, level and temporal sequence, as well as in the representations of binaural localization cues in both developing and adult animals. The neurodevelopmental aspects to these processes are essential; Bell et al (2008) have demonstrated that that sensory gating disruption during development can have both immediate and long-lasting effects on sensory-guided behavior. The ''deficient sensorimotor gating'' endophenotype, which leads to abnormalities in attention-associated information processes, bears much weight in the eventual staging of etiopathogenesis of disorder conditions ranging from Tourette's syndrome through attention-deficit hyperactivity disorder (ADHD) and Huntington's disease to schizophrenia.…”

Odor-specific habituation arises from interaction of afferent synaptic adaptation and intrinsic synaptic potentiation in olfactory cortex

“…Blockade of group III mGluR receptors prevents cortical adaptation odors (Best and Wilson 2004), and reduces short-term habituation of odor-evoked reflexes (Best et al 2005) and odor investigation (Yadon and Wilson 2005;Bell et al 2008;McNamara et al 2008). This short-term habituation is highly odor specific, with minimal cross-adaptation of piriform cortical single-unit responses or cross-habituation of behavioral responses to similar odors, including between mixtures and their components (Wilson 2000;Cleland et al 2002).…”