Cellular Prion Protein (PrP(C)) is known to mediate a protective role in several neurological conditions such as ischemia and epilepsy. However, so far, little information is available concerning the role of PrP(C) in psychiatric disorders such as depression. Here, we have used PrP(C) null mice to examine a putative role of PrP(C) in depressive-like states. Prion protein null mice exhibited depressive-like behaviour when compared to wild-type mice in both the Forced Swimming Test (FST) and Tail Suspension Test (TST). The clinical antidepressant drug imipramine and the NMDA receptor antagonist MK-801 reversed the depressive-like behaviour observed for knockout mice in the TST. The present data thus indicate that PrP(C) exerts a critical role in modulating the depressive-like state in mice, reinforcing the notion that PrP(C) might be associated with alterations in mood disorder states, and suggests a possible role of PrP(C) as a potential drug target for treating depressive disorders.
Behavior, Animal/physiology , Depression/metabolism , Exploratory Behavior/physiology , Motor Activity/drug effects , PrPC Proteins/metabolism , Animals , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Behavior, Animal/drug effects , Depression/drug therapy , Depression/genetics , Disease Models, Animal , Exploratory Behavior/drug effects , Hindlimb Suspension , Imipramine/pharmacology , Imipramine/therapeutic use , Mice , Mice, Knockout , Motor Activity/physiology , PrPC Proteins/genetics , Swimming
The auditory cortex (AC) is the major origin of descending auditory projections and is one of the targets of the cholinergic basal forebrain, nucleus basalis (NB). In the big brown bat, cortical activation evokes frequency-specific plasticity in the inferior colliculus and the NB augments this collicular plasticity. To examine whether cortical descending function and NB contributions to collicular plasticity are different between the bat and mouse and to extend the findings in the bat, we induced plasticity in the central nucleus of the mouse inferior colliculus by a tone paired with electrical stimulation of the NB (hereafter referred to as tone-ES(NB)). We show here that tone-ES(NB) shifted collicular best frequencies (BFs) towards the frequency of the tone paired with ES(NB) when collicular BFs were different from tone frequency. The shift in collicular BF was linearly correlated to the difference between collicular BFs and tone frequencies. The changes in collicular BFs after tone-ES(NB) were similar to those found in the big brown bat. Compared with cortical plasticity evoked by tone-ES(NB), the pattern of collicular BF shifts was identical but the shifting range of collicular BFs was narrower. A GABA(A) agonist (muscimol) or a muscarinic acetylcholine receptor antagonist (atropine) applied to the AC completely abolished the collicular plasticity evoked by tone-ES(NB). Therefore, our findings strongly suggest that the AC plays a critical role in experience-dependent auditory plasticity through descending projections.
Acoustic Stimulation/methods , Auditory Cortex/radiation effects , Auditory Pathways/physiology , Feedback/physiology , Inferior Colliculi/radiation effects , Neuronal Plasticity/radiation effects , Animals , Atropine/pharmacology , Auditory Cortex/physiology , Auditory Pathways/drug effects , Auditory Threshold/drug effects , Auditory Threshold/physiology , Auditory Threshold/radiation effects , Dose-Response Relationship, Radiation , Electric Stimulation/methods , Electroencephalography/methods , Evoked Potentials, Auditory/drug effects , Evoked Potentials, Auditory/physiology , Evoked Potentials, Auditory/radiation effects , Female , GABA Agonists/pharmacology , Inferior Colliculi/physiology , Mice , Mice, Inbred C57BL , Muscarinic Antagonists/pharmacology , Muscimol/pharmacology
