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.

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.Parkinson disease | deep brain stimulation | vesicular transporter | optogenetics | striatum T he subthalamic nucleus (STN) has long been a structure of interest for researchers and clinicians alike. There is ample evidence that high-frequency stimulation of the STN improves symptoms such as tremor, rigidity, and slowness of movement, so called bradykinesia, in patients with Parkinson disease (see ref. 1 for review), but the mechanism through which this is achieved is still unknown. Some studies suggest that electrical stimulation causes a hyperexcitation of this structure (2), whereas others find evidence that the opposite is true (3-5). Other possible interpretations include the activation of the zona incerta, a neighboring white-matter structure (6) or of fibers coming from the motor cortex (7). Bilateral lesions of the STN improve locomotion (8), a result that is consistent with the inactivation hypothesis. However, previous studies have also found cognitive side effects when using high-frequency stimulation of the STN (9), findings supported by lesion studies in experimental animals, which led to abnormalities in operant tasks involving attention and impulsivity (10, 11). The projections of the STN to other regions help explain the multiple roles of this structure: It sends projections to other targets in the basal ganglia, such as the internal segment of the globus pallidus [also termed the entopeduncular nucleus (EP) in rodents] and the substantia nigra pars reticulata (SNr) (12, 13). The STN is also part of a circuit that includes the prefrontal cortex and the nucleus accumbens (14). It is currently unknown, however, whether these different roles reflect a heterogeneous population of cells, characterized by distinct gene expression. If that is the case, it would allow direct control over each cell population, facilitating the investigation of their respective roles. In rodents, the S...

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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.

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.

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%, 10%, or 35% 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% EDC was not tested -or risk, although the results suggest that further tests are warranted.

it could be a result of different reactions to exposure to novel environments, or to a disturbed circadian rhythm (2). First, it should be established that the method through which we have measured locomotion-open field test, 1-h-long sessions during the dayis quite standard in the literature (see refs. 3 and 4 for recent examples involving knockout animals; further references are excluded because of space restrictions). In our analysis, using the open field test (in 2-d experiments), we chose to illustrate data in bar graphs in our original publication (1). However, we agree with Konsolaki and Skaliora (2) that it can be of interest to plot locomotion over time. In response to their comment, we therefore show here that by plotting locomotion (recorded as photobeam interruptions) vs. time (each 10 min) ( Fig. 1: preinjection data plotted over time provided as example), it is evident that both control and knockout mice decrease their activity with time, but that the locomotion of the knockout mice is higher than the controls throughout the test. Plotting the data in this way, thus, further supports our conclusion that the knockout mice show a hyperlocomotion phenotype. Furthermore, our data ( Fig. 1) appear similar to that in the example provided by Konsolaki and Skaliora ( figure 1B in ref. 2), which they choose to refer to as "genuine hyperlocomotion." Thus, we seem to agree that our knockout mice indeed are hyperlocomotive. Konsolaki and Skaliora further refer to what they find is an ambiguity in terms of experimental method; however, because we use a protocol of more than 1 d of testing, it follows that the environment is less new to the animals on the second compared with the first day of testing. Regarding circadian rhythm disturbances, Konsolaki and Skaliora (2) offer a single reference (5) for their claim that the subthalmic nucleus (STN) is involved in "sleep patterns," as they put it. This reference merely shows that c-fos activation of the STN is correlated with the sleep cycle and cites another study (6), which shows no alteration in the sleep-wake cycle after lesions of the STN. We do not believe there is adequate evidence to suggest that our results, which were collected at different points within the day-cycle, should be interpreted as a consequence of disturbances in the circadian rhythm.Our interpretation is based on a careful evaluation of the evidence we gathered, which shows that the STN was uniquely affected, with severe disturbances in the basal ganglia circuitry that complement our behavioral observations. As always, different interpretations are possible, and welcome, but we stand by our interpretation as expressed in our original paper (1): our intervention was the cause of a hyperlocomotive phenotype, explained by alterations in the STN and connected structures.

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