The auditory thalamus or medial geniculate body (MGB) is the final brain structure for acoustic information processing prior to, and functioning in reciprocity with, auditory cortex. MGB neurons process and gate aspects of acoustic stimuli, functions which depend partly on GABAergic inhibition. To characterize these properties, the inhibitory neurotransmitters involved and how they may be altered in the aged MGB, specific aims sought to: 1) determine the presence of functional high affinity GABAA receptors (GABAARs) in the MGB, 2) determine whether GABAAR function is altered with age and 3) determine to what degree MGB neurons of awake young and aged rats display stimulus-specific adaptation (SSA). Inhibitory neurotransmission is essential for accurate coding of acoustic information in the central auditory system, but appears disrupted in the aged. The present study required the development of a slice preparation that permitted whole cell recordings from juvenile, young adult and aged rat MGB neurons. The presence of high affinity GABAARs and the impact of aging on synaptic and high affinity GABAAR function were examined. Low concentrations of gaboxadol (GABAAR agonist) activated a gabazine-sensitive (GABAAR antagonist) tonic current, providing support for the expression of functional high affinity GABAARs in the MGB. Activation of high affinity GABAARs expressed by MGB neurons decreased input resistance, hyperpolarized resting membrane potential, reduced evoked firing rates and induced a transition from tonic to burst firing mode. In aged MGB neurons there was a significant 50.4% reduction in GABAAR-mediated tonic Cl- current. Synaptic GABAAR inhibition appeared differentially affected by age in lemniscal and non-lemniscal auditory thalamus although gramicidin perforated patch-clamp recordings indicated neuronal Cl- homeostasis was unaltered with age. Anesthetized rodent MGB single units show SSA, during which the firing rate in response to repetitive stimuli decreases/adapts over time but low probability stimuli (i.e. novel) continue to elicit robust responses. To examine the presence of SSA in the MGB of awake rats, a multichannel single unit recording preparation was implemented. This approach involved implanting young and aged rats with an array of four individually-advanceable tetrodes in order to evaluate SSA by recording responses to a frequency oddball paradigm and a random/non-random frequency range paradigm. Single units in the MGB of awake FBN rats were found to display SSA, which was stronger in the non-lemniscal than lemniscal regions of the MGB. SSA was most dramatic at lower intensities where 27 of 57 (47%) young adult single units and 28 of 54 (52%) aged single units displayed SSA. However, there were no significant age-related differences in average magnitude or time course of SSA of MGB single units studied. Data from aims 1 and 2 provide the initial description of functional high affinity GABAARs in the rodent MGB and the plasticity of these receptors with age. These data suggest that GABAAR subtype-selective agonists or modulators could be used to augment MGB inhibitory neurotransmission, possibly improving speech understanding for a subset of elderly individuals. Findings from aim 3 were the first to show that SSA by MGB neurons is not dependent on arousal level nor on the anesthetized state, but is a common response in the MGB of awake rats. SSA did not appear to be overtly altered in the aged auditory thalamus of awake rats.

The goal of this thesis is to investigate the functional role of the cortical column architecture within some of the existing brain coding theories. Here I focus on the hierarchical models of predictive coding and the 'phase of firing' coding hypothesis. Using an oddball paradigm consisting of a sequence of identical sounds interspersed with rare, unexpected sounds, one can observe a difference between the scalp potentials evoked by oddball and common sounds. This difference has been linked to predictive coding and novelty detection, and Stimulus Specific Adaptation (SSA) has been suggested as a likely substrate at the single neuron level. In order to simultaneously constrain hierarchical models of predictive coding, and so as to investigate the contributions that neural processing within the different cytoarchitectonic layers of the primary auditory cortex (A1) may make to SSA, I simultaneously recorded multi-unit activity and current source density (CSD) profiles across all layers in A1 of the rat in response to standard and oddball tones. Our results suggest that SSA arises at the level of the thalamocortical synapse and is further enhanced in the supragranular layers. The phase of low-frequency Local Field Potentials (LFPs) in primary sensory cortices carries stimulus related information and disambiguates the information about different stimuli evoking similar spike rates. However, it is yet unclear how these informative LFP phase values arise within the laminar organization of cortical columns. To address this issue, I performed CSD recordings in the area A1 of anaesthetized rats during the presentation of complex naturalistic sounds. Information theoretic analysis revealed that most LFP phase information originates from discrete CSD events consisting of strong granular-superficial-layer dipoles, likely triggered by bursts of thalamocortical activation. These events, which occur at rates of 2-4 Hz, reliably reset LFP phases at times of strong network excitation. They therefore provide a useful reference frame to measure neural activity with respect to salient times of stimulus history. CSD events display a diverse, stimulus-dependent morphology: these reflect the outcomes of cortical computations which result in varying extents of activation of infragranular output layers.