Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion.

The subthalamic nucleus (STN) is a key area of the basal ganglia circuitry regulating movement. We identified a subpopulation of neurons within this structure that coexpresses Vglut2 and Pitx2, and by conditional targeting of this subpopulation we reduced Vglut2 expression levels in the STN by 40%, leaving Pitx2 expression intact. This reduction diminished, yet did not eliminate, glutamatergic transmission in the substantia nigra pars reticulata and entopeduncular nucleus, two major targets of the STN. The knockout mice displayed hyperlocomotion and decreased latency in the initiation of movement while preserving normal gait and balance. Spatial cognition, social function, and level of impulsive choice also remained undisturbed. Furthermore, these mice showed reduced dopamine transporter binding and slower dopamine clearance in vivo, suggesting that Vglut2-expressing cells in the STN regulate dopaminergic transmission. Our results demonstrate that altering the contribution of a limited population within the STN is sufficient to achieve results similar to STN lesions and high-frequency stimulation, but with fewer side effects.

Ventral hippocampal OLM cells control type 2 theta oscillations and response to predator odor.

Dorsal and ventral hippocampus regions exert cognition and emotion-related functions, respectively. Since both regions display rhythmic activity, specific neural oscillatory pacemakers may underlie their functional dichotomy. Type 1 theta oscillations are independent of cholinergic transmission and are observed in the dorsal hippocampus during movement and exploration. In contrast, type 2 theta depends on acetylcholine and appears when animals are exposed to emotionally laden contexts such as a predator presence. Despite its involvement in emotions, type 2 theta has not been associated with the ventral hippocampus. Here, we show that optogenetic activation of oriens-lacunosum moleculare (OLM) interneurons in the ventral hippocampus drives type 2 theta. Moreover, we found that type 2 theta generation is associated with increased risk-taking behavior in response to predator odor. These results demonstrate that two theta oscillations subtypes originate in the two hippocampal regions that predominantly underlie either cognitive or emotion-related functions.

On the photovoltaic effect in local field potential recordings.

Optogenetics allows light activation of genetically defined cell populations and the study of their link to specific brain functions. While it is a powerful method that has revolutionized neuroscience in the last decade, the shortcomings of directly stimulating electrodes and living tissue with light have been poorly characterized. Here, we assessed the photovoltaic effects in local field potential (LFP) recordings of the mouse hippocampus. We found that light leads to several artifacts that resemble genuine LFP features in animals with no opsin expression, such as stereotyped peaks at the power spectrum, phase shifts across different recording channels, coupling between low and high oscillation frequencies, and sharp signal deflections that are detected as spikes. Further, we tested how light stimulation affected hippocampal LFP recordings in mice expressing channelrhodopsin 2 in parvalbumin neurons (PV/ChR2 mice). Genuine oscillatory activity at the frequency of light stimulation could not be separated from light-induced artifacts. In addition, light stimulation in PV/ChR2 mice led to an overall decrease in LFP power. Thus, genuine LFP changes caused by the stimulation of specific cell populations may be intermingled with spurious changes caused by photovoltaic effects. Our data suggest that care should be taken in the interpretation of electrophysiology experiments involving light stimulation.

Cre-driven optogenetics in the heterogeneous genetic panorama of the VTA.

The selectivity of optogenetics commonly relies on genetic promoters to manipulate specific populations of neurons through the use of Cre-driver lines. All studies performed in the ventral tegmental area (VTA) so far have utilized promoters present in groups of cells that release dopamine (DA), GABA, or glutamate. However, neurons that co-release neurotransmitters and variabilities within groups of neurons that release the same neurotransmitter present challenges when evaluating the results. Further complexity is introduced by ectopic expression patterns often occurring in transgenic Cre-drivers. New perspectives could be unfolded by identifying and selecting different types of promoter for driving the Cre recombinase. Here, we discuss some promising candidates and highlight the advantages or disadvantages of different methods for creating novel transgenic lines.

Attention, locomotor activity and developmental milestones in rats prenatally exposed to ethanol.

RATIONALE: Decline of attentional performance as a function of time engaged on a task and hyperactivity are features shared by children and adults with fetal alcohol syndrome or attentional deficit and hyperactivity disorders. OBJECTIVE: To investigate the effects of prenatal exposure to two doses of ethanol on developmental milestones, locomotor activity and attention. METHODS: Wistar rats born from dams exposed to one of four maternal treatments during pregnancy were used: A35 - liquid diet with 35% ethanol-derived calories; A10 - liquid diet with 10% ethanol-derived calories; control - ethanol-free liquid diet; chow - laboratory chow and water. RESULTS: A35 performed worse in grip strength than control and chow (postnatal day - 14, p<0.05) but not in negative geotaxis (postnatal days 7-10); A35 also showed more locomotor activity than control and A10 (p<0.05). Regarding attention, acquisition of the five choice reaction time task was similar between groups, but, the percentage of omission errors from A35 group was greater than other groups at baseline parameters, at shorter (2s) and longer (7s) inter-trial intervals and at a shorter stimulus duration (0.5s) (p<0.05). The percentage of omissions was larger in A35 as the blocks progressed in sessions with either longer or shorter inter-trial intervals (group×block p<0.05). Animals from A10 group did not show any impairment in the tasks performed. CONCLUSIONS: Our study demonstrates that as well as developmental impairments, prenatal ethanol can produce deficits associated with an increase in attentional demand in rodents, analogous to those observed in fetal alcohol syndrome and attentional deficit and hyperactivity disorders.

Prenatal alcohol exposure did not affect impulsivity in rats that performed delay or probability discounting tasks

Individuals who fall under the spectrum of the Fetal Alcohol Syndrome have a higher prevalence of several cognitive disturbances, including a greater probability of being diagnosed with attention-deficit hyperactivity disorder (ADHD). Some of these effects, such as hyperactivity and attentional impairments, are already well established in the literature. The assessment of impulsive choice, however, has received little attention in human and animal studies. In the present study, we attempted to investigate the effects of prenatal ethanol exposure on two tasks related to impulsive choice that have never been studied in this condition: delay and probability discounting. METHOD: Rats prenatally exposed to ethanol (liquid diets with 0 percent, 10 percent, or 35 percent ethanol-derived calories [EDC] or laboratory chow) were trained to respond for food in either delay (n = 21) or probability (n = 48) discounting tasks performed in computer-controlled operant conditioning chambers. RESULTS: Prenatal treatment failed to differentiate the rates at which the rats chose the larger reinforcer associated with delay - in a task in which 35 percent EDC was not tested - or risk, although the results suggest that further tests are warranted.