Neurotrophin receptor activation rescues cognitive and synaptic abnormalities caused by hemizygosity of the psychiatric risk gene Cacna1c.

Genetic variation in CACNA1C, which encodes the alpha-1 subunit of Ca1.2 L-type voltage-gated calcium channels, is strongly linked to risk for psychiatric disorders including schizophrenia and bipolar disorder. To translate genetics to neurobiological mechanisms and rational therapeutic targets, we investigated the impact of mutations of one copy of Cacna1c on rat cognitive, synaptic and circuit phenotypes implicated by patient studies.

Cyfip1 haploinsufficient rats show white matter changes, myelin thinning, abnormal oligodendrocytes and behavioural inflexibility.

The biological basis of the increased risk for psychiatric disorders seen in 15q11.2 copy number deletion is unknown. Previous work has shown disturbances in white matter tracts in human carriers of the deletion.

Genetic Variation in the Psychiatric Risk Gene CACNA1C Modulates Reversal Learning Across Species.

Genetic variation in CACNA1C, which encodes the alpha-1 subunit of Cav1.2 L-type voltage-gated calcium channels (VGCCs), has been strongly linked to risk for psychiatric disorders including schizophrenia and bipolar disorder. How genetic variation in CACNA1C contributes to risk for these disorders is however not fully known.

Conditioning with spatio-temporal patterns: Constraining the contribution of the hippocampus to configural learning.

The conditions under which the hippocampus contributes to learning about spatio-temporal configural patterns are not fully established. The aim of Experiments 1-4 was to investigate the impact of hippocampal lesions on learning about where or when a reinforcer would be delivered. In each experiment, the rats received exposure to an identical set of patterns (i.

Mediated configural learning in rats.

Three experiments investigated mediated configural learning in male rats. In Experiment 1, after exposure to audio-visual compounds AX and BY, rats received trials where X was paired with shock, and Y was not. The idea that conditioning with X enables the evoked configural representation of AX to be linked to shock received support from the facts that while AX provoked more fear than BX, there was no difference between BY and AY.

Novel sensory preconditioning procedures identify a specific role for the hippocampus in pattern completion.

Successful retrieval of a memory for an entire pattern of stimulation by the presentation of a fragment of that pattern is a critical facet of memory function. We examined processes of pattern completion using novel sensory preconditioning procedures in rats that had either received sham lesions (group Sham) or lesions of the hippocampus (group HPC). After exposure to two audio-visual patterns (AX and BY) rats received fear conditioning with X (but not Y).

Configural integration of temporal and contextual information in rats: Automated measurement in appetitive and aversive preparations.

Two experiments investigated the capacity of rats to learn configural discriminations requiring integration of contextual (where) with temporal (when) information. In Experiment 1, during morning training sessions, food was delivered in context A and not in context B, whereas during afternoon sessions food was delivered in context B and not in context A. Rats acquired this discrimination over the course of 20 days.

Assessing the encoding specificity of associations with sensory preconditioning procedures.

Three experiments examined the encoding specificity of associations using sensory preconditioning procedures in rats. In Experiment 1a, after exposure to two compounds (AX and BY), X (but not Y) was either followed by shock after a trace interval (Group Trace) or immediately followed by shock (Group Immediate). AX elicited less activity than BX (i.

Evidence that the rat hippocampus has contrasting roles in object recognition memory and object recency memory.

Adult rats with extensive, bilateral neurotoxic lesions of the hippocampus showed normal forgetting curves for object recognition memory, yet were impaired on closely related tests of object recency memory. The present findings point to specific mechanisms for temporal order information (recency) that are dependent on the hippocampus and do not involve object recognition memory. The object recognition tests measured rats exploring simultaneously presented objects, one novel and the other familiar.

Encoding specific associative memory: evidence from behavioral and neural manipulations.

Within-subjects procedures with rats assessed the associative structures acquired during conditioning trials in which the interval between the stimuli and food was either short or long (i.e., A-10 s→food and B-40 s→food).

Analysis of the content of configural representations: the role of associatively evoked and trace memories.

Two experiments examined the content of configural learning in rats. In Experiment 1, after simple pre-exposure to two hybrid contexts (AB and CD), rats acquired a configural discrimination involving two of the contexts (A and C) and two auditory stimuli (X and Y; AX→food, AY→no food, CX→no food, and CY→food). When rats were then placed in context B, they were more likely to respond to X than Y, and when they were placed in context D the reverse was the case.