Memory Consolidation for the Discrimination of Frequency-Modulated Tones in Mongolian Gerbils Is Sensitive to Protein-Synthesis Inhibitors Applied to the Auditory Cortex

Abstract

Differential conditioning of Mongolian gerbils to linearly frequency-modulated tones (FM) has recently received experimental attention. In the study of the role of cerebral protein synthesis for FM discrimination memory, gerbils received post-training bilateral injections of anisomycin into the auditory cortex under light halothane anesthesia. Compared with saline-treated controls, anisomycin-treated gerbils showed a discrimination decrement during the subsequent three days of training. They markedly improved their performance within training sessions, but started each session at low levels. When repeatedly trained gerbils received post-session injections of anisomycin, discrimination performance during subsequent sessions was similar to the pre-injection performance, indicating that retention, retrieval, reconsolidation, and expression of the established reaction were not affected. However, the improvement of a partially established discrimination reaction was impaired after this treatment. Intracortical injections of emetine confirmed this finding. Neither drug affected FM discrimination learning when given several days before the initial training. Our results suggest that protein-synthesis inhibitors applied to the auditory cortex of gerbils during the post-acquisition phase interfered with learning and memory-related aspects of FM processing. The resulting deficit was evident for a number of post-injection training days. This effect was probably due to impaired consolidation, i.e., processes required for long-term stabilization or retrieval of the memory trace while leaving short-term memory intact.

Dopamine-Modulated Recurrent Corticoefferent Feedback in Primary Sensory Cortex Promotes Detection of Behaviorally Relevant Stimuli

“…The increased correlation at a relative synaptic delay of ϳ6 ms provides a first indication of a positive feedback routed from deeper cortical layers back to cortical input layers. Given that D 1 /D 5 receptors are predominantly located in (Campbell et al, 1987;Phillipson et al, 1987;Krimer et al, 1997;Schicknick et al, 2008), and that local intracortical routing of recurrent microcircuits in AI (Liu et al, 2007) is characterized by shorter synaptic delays of 0.8 -1.0 ms per cortical synapse (Tsumoto and Suda, 1982), these findings are compatible with a polysynaptic routing of the feedback via relays outside the analyzed cortical area. The following sections describe a stepwise procedure to find support for this hypothesis and rule out alternative interpretations on a cortical circuit level.…”

“…Intracortical activity was blocked in the electrical stimulation experiments by epidural application of the GABA A agonist muscimol hydrobromide (Sigma), 20 l muscimol alone with concentrations varied between 0.2 and 1.0 g/l (n ϭ 10) or concomitantly applied with GABA B receptor agonist (ϩ)-5,5-dimethyl-2-morpholine acetic acid (SCH50911; 6 mM, 20 l, n ϭ 2) to block GABA B -mediated presynaptic inhibition of thalamocortical synapses by muscimol effects on GABA B receptors (Liu et al, 2007). We did not find any differences between these methods; for further information on the adequacy of different silencing techniques, see also Happel et al, 2010.…”

“…While the neuromodulatory actions of dopamine are increasingly well characterized in prefrontal cortical and midbrain neuronal circuits (Tritsch and Sabatini, 2012), the consequences of dopaminergic modulations in primary sensory areas are less well understood. Dopaminergic fibers and D 1 /D 5 receptors are most abundant in the infragranular output layers V and VI across species in primary auditory cortex (Campbell et al, 1987;Phillipson et al, 1987;Schicknick et al, 2008) and other cortices (Krimer et al, 1997). Therefore, it could be hypothesized that dopamine intracortically released in infragranular layers unfolds its action by modulating the infragranular corticoefferent output of the cortical circuitry (Phillipson et al, 1987).…”

“…Using a cortex-dependent auditory learning paradigm (Ohl et al, 1999), it was previously shown that long-term memory formation depends on transient and local intracortical dopamine release (Stark and Scheich, 1997; mediating protein synthesis-dependent plasticity in auditory cortex (Kraus et al, 2002;Schicknick et al, 2008Schicknick et al, , 2012. While the neuromodulatory actions of dopamine are increasingly well characterized in prefrontal cortical and midbrain neuronal circuits (Tritsch and Sabatini, 2012), the consequences of dopaminergic modulations in primary sensory areas are less well understood.…”

Enhanced cognitive flexibility in reversal learning induced by removal of the extracellular matrix in auditory cortex

“…In this respect, our findings support recent hypotheses emphasizing dynamic ECM changes in the adult brain to adeptly stabilize or free synaptic networks on a short time scale. Such processes might titrate longterm stability of memory content and its activity-dependent reorganization (2,16,22).…”