Delta-frequency stimulation of cerebellar projections can compensate for schizophrenia-related medial frontal dysfunction.

Schizophrenia involves abnormalities in the medial frontal cortex that lead to cognitive deficits. Here we investigate a novel strategy to normalize medial frontal brain activity by stimulating cerebellar projections. We used an interval timing task to study elementary cognitive processing that requires both frontal and cerebellar networks that are disrupted in patients with schizophrenia. We report three novel findings. First, patients with schizophrenia had dysfunctional delta rhythms between 1-4 Hz in the medial frontal cortex. We explored cerebellar-frontal interactions in animal models and found that both frontal and cerebellar neurons were modulated during interval timing and had delta-frequency interactions. Finally, delta-frequency optogenetic stimulation of thalamic synaptic terminals of lateral cerebellar projection neurons rescued timing performance as well as medial frontal activity in a rodent model of schizophrenia-related frontal dysfunction. These data provide insight into how the cerebellum influences medial frontal networks and the role of the cerebellum in cognitive processing.

High-gamma band fronto-temporal coherence as a measure of functional connectivity in speech motor control.

The neural basis of human speech is unclear. Intracranial electrophysiological recordings have revealed that high-gamma band oscillations (70-150Hz) are observed in the frontal lobe during speech production and in the temporal lobe during speech perception. Here, we tested the hypothesis that the frontal and temporal brain regions had high-gamma coherence during speech. We recorded electrocorticography (ECoG) from the frontal and temporal cortices of five humans who underwent surgery for medically intractable epilepsy, and studied coherence between the frontal and temporal cortex during vocalization and playback of vocalization. We report two novel results. First, we observed high-gamma band as well as theta (4-8Hz) coherence between frontal and temporal lobes. Second, both high-gamma and theta coherence were stronger when subjects were actively vocalizing as compared to playback of the same vocalizations. These findings provide evidence that coupling between sensory-motor networks measured by high-gamma coherence plays a key role in feedback-based monitoring and control of vocal output for human vocalization.

Prefrontal D1 dopamine signaling is necessary for temporal expectation during reaction time performance.

Responses during a simple reaction time task are influenced by temporal expectation, or the ability to anticipate when a stimulus occurs in time. Here, we test the hypothesis that prefrontal D1 dopamine signaling is necessary for temporal expectation during simple reaction time task performance. We depleted dopamine projections to the medial prefrontal circuits by infusing 6-hydroxidopamine, a selective neurotoxin, into the ventral tegmental area (VTA) of rats, and studied their performance on a simple reaction time task with two delays. VTA dopamine depletion did not change movements or learning of the reaction time task. However, VTA dopamine-depleted animals did not develop delay-dependent speeding of reaction times, suggesting that mesocortical dopamine signaling is required for temporal expectation. Next, we manipulated dopamine signaling within the medial prefrontal cortex using local pharmacology. We found that SCH23390, a D1-type dopamine receptor antagonist, specifically attenuated delay-dependent speeding, while sulpiride, a D2-type receptor antagonist, did not. These data suggest that prefrontal D1 dopamine signaling is necessary for temporal expectation during performance of a simple reaction time task. Our findings provide insight into temporal processing of the prefrontal cortex, and how dopamine signaling influences prefrontal circuits that guide goal-directed behavior.

Plasmon-tuned silver colloids for SERRS analysis of methemoglobin with preserved nativity.

Optically tuned silver nanoparticles (AgNP's) functionalized with ω-mercaptoalkanoic acids are synthesized and used as a signal amplifier for the surface-enhanced resonance Raman scattering (SERRS) study of heme cofactor in methemoglobin (metHb). Even though both mercaptopropionic acid (MPA)- and mercaptononanoic acid (MNA)-functionalized AgNP's exemplify vastly enhanced SERRS signal of metHb, MNA-AgNP's amplify the SERRS signal amid preservation of the nativity of the heme pocket, unlike MPA-AgNP's. The electrostatic interaction between MNA-AgNP's and metHb leads to instant signal enhancement with a Raman enhancement factor (EF(SERS)) of 4.2 × 10(3). Additionally, a Langmuir adsorption isotherm has been employed for the adsorption of metHb on the MNA-AgNP surface, which provides the real surface coverage and equilibrium constant (K) of metHb as 139 nM and 3.6 × 10(8) M(-1), respectively. The lowest detection limit of 10 nM for metHb has been demonstrated using MNA-AgNP's besides retaining the nativity of the heme pocket.

Ambient temperature, zinc ion-conducting, binary molten electrolyte based on acetamide and zinc perchlorate: Application in rechargeable zinc batteries.

Binary room temperature molten electrolytes based on acetamide and zinc perchlorate have been prepared and characterized. The electrolytes are found to be highly zinc ion-conducting with very favorable physicochemical and electrochemical characteristics. Raman and infrared spectroscopic studies reveal the presence of large free-ion concentration in the molten liquid. This is corroborated by the high conductivity observed under ambient conditions. Rechargeable zinc batteries assembled using gamma-MnO(2) as the cathode and Zn as the anode with the molten electrolyte show high discharge capacities over several cycles, indicating excellent reversibility. This unique class of acetamide-based, room temperature molten liquids may become viable and green alternative electrolytes for rechargeable zinc-based secondary batteries.

Reversible inactivations of rat medial prefrontal cortex impair the ability to wait for a stimulus.

In simple reaction time tasks, lesions of rat dorsomedial prefrontal cortex impair the ability to wait for trigger stimuli and result in increased premature responding. This effect could be due to impairments in attending to trigger stimuli, estimating the timing of trigger stimuli, or inhibitory control of the motor response. Here, we examined these issues by reversibly inactivating dorsomedial prefrontal cortex during simple reaction time tasks with variable or fixed foreperiods. There were three consistent effects of dorsomedial prefrontal cortex inactivation: 1) increased premature responding, 2) increased variability in the timing of premature responses, and 3) speeded response latencies, especially on trials with short foreperiods in tasks with variable foreperiods. We observed these effects independent of differences in foreperiod duration, foreperiod variability, and stimulus probabilities. Therefore, dorsomedial prefrontal cortex appears not to be involved in attending to the trigger stimulus or in time estimation. Instead, we suggest that dorsomedial prefrontal cortex is critical for inhibiting responses before the maximum foreperiod duration, i.e. the "deadline" [Ollman RT, Billington MJ (1972) The deadline model for simple reaction times. Cognit Psychol 3:311-336], after which the rat should respond even if the trigger stimulus has not occurred.

Interaction between cigarette smoke condensate and radiation for the induction of genotoxic effects in yeast.

Induction of gene conversion in diploid yeast strains BZ34 and D7 was investigated following exposure to cigarette smoke condensate (CSC) and gamma radiation. Cells treated with CSC for 1 h showed 5-10-fold increase in gene conversion over the background frequency. Log-phase cells were 2-3 times more sensitive compared to stationary-phase cells. Cells exposed to a combination of CSC and radiation suggested an additive response of the 2 agents, irrespective of the order of the 2 treatments.