Evoked responses to single pulse electrical stimulation reveal impaired striatal excitability in a rat model of Parkinson's disease.

Background: Sensorimotor beta oscillations are increased in Parkinson's disease (PD) due to the alteration of dopaminergic transmission. This electrophysiological read-out is reported both in patients and in animal models such as the 6-OHDA rat model obtained with unilateral nigral injection of 6-hydroxydopamine (6-OHDA). Current treatments, based on dopaminergic replacement, transiently normalize this pathological beta activity and improve patients' quality of life.

Single-pulse electrical stimulation methodology in freely moving rat.

Background: Cortico-cortical evoked potentials (CCEP) are becoming popular to infer brain connectivity and cortical excitability in implanted refractory epilepsy patients. Our goal was to transfer this methodology to the freely moving rodent.

New Method: CCEP were recorded on freely moving Sprague-Dawley rats, from cortical and subcortical areas using depth electrodes.

Prefrontal Theta Oscillations Promote Selective Encoding of Behaviorally Relevant Events.

The ability to capture the most relevant information from everyday experiences without constantly learning unimportant details is vital to survival and mental health. While decreased activity of the medial prefrontal cortex (mPFC) is associated with failed or inflexible encoding of relevant events in the hippocampus, mechanisms used by the mPFC to discern behavioral relevance of events are not clear. To address this question, we chemogenetically activated excitatory neurons in the mPFC of male rats and examined its impact on local network activity and differential associative learning dependent on the hippocampus.

Deep brain stimulation and fluoxetine exert different long-term changes in the serotonergic system.

Both selective serotonin reuptake inhibitors (SSRIs) and ventromedial prefrontal cortex (vmPFC) deep brain stimulation (DBS) modulate serotonergic activity. We compared the acute (1 day) and long-term (12 days) effects of vmPFC stimulation and fluoxetine on serotonin (5-HT) release and receptor expression in rats. Samples to measure serotonin levels were collected from the hippocampus using microdialysis.

Deep brain stimulation induces antidepressant-like effects in serotonin transporter knockout mice.

Background: Some of the antidepressant-like effects of ventromedial prefrontal cortex (vmPFC) deep brain stimulation (DBS) in rodents have been attributed to the modulation of prefrontal-raphe pathways. This is largely different from selective serotonin reuptake inhibitors (SSRIs), which increase serotonin (5-HT) levels by inhibiting the serotonin transporter (SERT). SSRIs have limited efficacy when given to SERT knockout (KO) mice, or patients with mutations in the serotonin transporter promoter gene (5-HTTLPR).

Enhancing Prefrontal Neuron Activity Enables Associative Learning of Temporally Disparate Events.

The ability to link events that are separated in time is important for extracting meaning from experiences and guiding behavior in the future. This ability likely requires the brain to continue representing events even after they have passed, a process that may involve the prefrontal cortex and takes the form of sustained, event-specific neuron activity. Here, we show that experimentally increasing the activity of excitatory neurons in the medial prefrontal cortex (mPFC) enables rats to associate two stimuli separated by a 750-ms long temporal gap.

Cholinergic, but not NMDA, receptors in the lateral entorhinal cortex mediate acquisition in trace eyeblink conditioning.

Anatomical and electrophysiological studies collectively suggest that the entorhinal cortex consists of several subregions, each of which is involved in the processing of different types of information. Consistent with this idea, we previously reported that the dorsolateral portion of the entorhinal cortex (DLE), but not the caudomedial portion, is necessary for the expression of a memory association between temporally discontiguous stimuli in trace eyeblink conditioning (Morrissey et al. (2012) J Neurosci 32:5356-5361).

Reduced expression of STOP/MAP6 in mice leads to cognitive deficits.

Background: STOP/MAP6 null (KO) mice recapitulate behavioral abnormalities related to positive and negative symptoms and cognitive deficits of schizophrenia. Here, we investigated whether decreased expression of STOP/MAP6 proteins in heterozygous mice (only one allele expressed) would result in abnormal behavior related to those displayed by STOP null mice.

Methods: Using a comprehensive test battery, we investigated the behavioral phenotype of STOP heterozygous (Het) mice compared with STOP KO and wild type (WT) mice on animals raised either in standard conditions (controls) or submitted to maternal deprivation.

Longitudinal MRI monitoring of brain damage in the neonatal ventral hippocampal lesion rat model of schizophrenia.

Rat with excitotoxic neonatal ventral hippocampal lesions (NVHL rats) is considered as a heuristic neurodevelopmental model for studying schizophrenia. Extensive study of this model is limited by the lack of clear validity criteria of such lesions and because ascertaining of the lesions is realized postmortem with histological examination after completing experiments. Here, in a first experiment, by assessing the locomotor response to amphetamine in adult NVHL rats, we further specify that the lesions must be bilateral and confined to the ventral hippocampus to obtain the validated behavioral phenotype.