Auditory steady-state responses in the auditory cortex of mice during estrus cycle.

Auditory-steady state responses (ASSRs) disclose the brain's potency to oscillate and have been suggested to serve as biomarkers in various psychiatric disorders. GABAergic neurotransmission, a critical component of brain oscillations, is strongly influenced by sex hormones. In line, the severity of symptoms in psychiatric disorders has been linked to changes in sex hormones during the menstrual cycle. However, how these sex hormones affect ASSRs remain largely unknown. This was addressed by performing chronic recordings of ASSRs in mice while monitoring its estrus cycle. Here, the stability of ASSRs during long-term recordings was validated and showed good reliability. 40 Hz ASSRs showed changes throughout the estrus cycle where it decreased in the metestrus phase compared to the diestrus phase. In contrast, other frequency ASSRs did not show significant changes throughout the estrus cycle. Taken together, our findings illustrate that the estrus cycle may influence the generation of ASSRs and that the phase of the estrus cycle should be taken into consideration when ASSRs are recorded in females.

Sex differences in serotonergic control of rat social behaviour.

RATIONALE: There is increasing evidence that enhancement of the salience of social stimuli can have a beneficial effect in managing many psychiatric conditions. There are, however, clear sex-related differences in social behaviour, including the neural mechanisms responsible for different aspects of social functions. OBJECTIVES: We explored the role of the serotonergic system on rat social behaviour under baseline and under stressful conditions in female and male rats. METHODS: Rats were treated with the selective serotonin transporter (SERT) inhibitor escitalopram postnatally; a procedure known to cause a long-lasting reduction of serotonergic activity. In adulthood, social behaviour was tested in a social interaction test and in ultrasonic vocalisation (USVs) recording sessions before and after yohimbine-induced stress-like state. RESULTS: Our data demonstrated that both female and, to a lesser extent, male escitalopram treated rats, exposed to a novel social situation, had fewer social exploration events and emitted fewer frequency-modulated calls with trills, trills and step calls, suggesting that an impaired function of the serotonergic system reduced the positive valence of social interaction. In a stress-like state, 50 kHz flat calls were increased only in female rats, indicating an increased seeking of social contact. However, the number of flat calls in escitalopram treated female rats was significantly lower compared with control rats. CONCLUSIONS: These data suggest that females may respond differently to serotonergic pharmacotherapy with respect to enhancement of beneficial effects of social support, especially in stress-related situations.

Melatonin Reduces Alcohol Drinking in Rats with Disrupted Function of the Serotonergic System.

The reason for the limited treatment success of substance-use-related problems may be a causal heterogeneity of this disorder that, at least partly, is manifested as differences in substance-use motives between individuals. The aim of the present study was to assess if rats with pharmacologically induced differences in the function of the serotonergic system would respond differently to melatonin treatment compared to control rats with respect to voluntary alcohol consumption. To achieve this goal, we treated rats neonatally with the selective serotonin transporter (SERT) inhibitor escitalopram. This procedure has been reported to cause long-lasting sleep abnormalities in rodents. The study demonstrated that during adulthood, rats that had been treated with escitalopram tended to drink higher amounts of alcohol compared to control rats. Further, administration of melatonin significantly decreased the alcohol intake in escitalopram-treated animals but caused only a slight, nonsignificant reduction in the alcohol consumption by control rats. In conclusion, our data support the therapeutic potential of melatonin as a treatment for alcohol use disorder. However, interindividual differences between alcohol users may considerably modify the outcome of the melatonin treatment, whereby patients that manifest lower sleep quality due to disruption of serotonergic activity are more likely to benefit from this treatment.

The Anticonvulsant Lamotrigine Reduces Bout-Like Alcohol Drinking in Rats.

We used an optical lickometer system to study drinking microstructure and effect of lamotrigine in voluntary alcohol-drinking rats. We showed that, similar to humans, animals differ by their drinking microstructure where some consume alcohol exclusively in a bout-like patterns. The study suggests that anticonvulsants, such as lamotrigine, may be one treatment strategy specifically affecting this type of drinking.

Effect of ethanol on the visual-evoked potential in rat: dynamics of ON and OFF responses.

The effect of acute ethanol administration on the flash visual-evoked potential (VEP) was investigated in numerous studies. However, it is still unclear which brain structures are responsible for the differences observed in stimulus onset (ON) and offset (OFF) responses and how these responses are modulated by ethanol. The aim of our study was to investigate the pattern of ON and OFF responses in the visual system, measured as amplitude and latency of each VEP component following acute administration of ethanol. VEPs were recorded at the onset and offset of a 500 ms visual stimulus in anesthetized male Wistar rats. The effect of alcohol on VEP latency and amplitude was measured for one hour after injection of 2 g/kg ethanol dose. Three VEP components - N63, P89 and N143 - were analyzed. Our results showed that, except for component N143, ethanol increased the latency of both ON and OFF responses in a similar manner. The latency of N143 during OFF response was not affected by ethanol but its amplitude was reduced. Our study demonstrated that the activation of the visual system during the ON response to a 500 ms visual stimulus is qualitatively different from that during the OFF response. Ethanol interfered with processing of the stimulus duration at the level of the visual cortex and reduced the activation of cortical regions.

The influence of increased membrane conductance on response properties of spinal motoneurons.

During functional spinal neural network activity motoneurons receive massive synaptic excitation and inhibition, and their membrane conductance increases considerably - they are switched to a high-conductance state. High-conductance states can substantially alter response properties of motoneurons. In the present study we investigated how an increase in membrane conductance affects spike frequency adaptation, the gain (i.e., the slope of the frequency-current relationship) and the threshold for action potential generation. We used intracellular recordings from adult turtle motoneurons in spinal cord slices. Membrane conductance was increased pharmacologically by extracellular application of the GABAA receptor agonist muscimol. Our findings suggest that an increase in membrane conductance of about 40-50% increases the magnitude of spike frequency adaptation, but does not change the threshold for action potential generation. Increased conductance causes a subtractive rather than a divisive effect on the initial and the early frequency-current relationships and may have not only a subtractive but also a divisive effect on the steady-state frequency-current relationship.

Gain of spinal motoneurons measured from square and ramp current pulses.

The gain of motoneurons (MNs) characterizes how variations in synaptic input are transformed in to variations in output firing and muscle contraction. Experimentally gain is often defined as the frequency-current relation observed in response to injected suprathreshold square current pulses or current ramps during intracellular recording. The gain of MNs is strongly affected by adaptation: transient gain in response to depolarization is usually higher than steady state gain measured during sustained depolarization. The transient and the stationary gain of neurons are separate entities that can be selectively modified. Here we investigated how the transient and the stationary gain of spinal MNs obtained from responses to square current pulses are related to gain estimated from the responses to the current ramps. We found, that the gain in response to current ramps is identical to the steady state gain during sustained depolarization. Therefore, gain modulation is more fully characterized with square current pulses than with current ramps.

Persistent sodium current decreases transient gain in turtle motoneurons.

Voltage dependent ion channels can influence signal integration in neurons dramatically. In addition to the classical fast-inactivating Na(+) current that mediates action potentials, many neurons also express persistent sodium current (I(NaP)). Activating at membrane potentials below the threshold for action potentials, this current may amplify excitatory postsynaptic potentials and shape the firing patterns. To determine the qualitative contribution of I(NaP) to the intrinsic firing properties of motoneurons, we eliminated this current by dynamic clamp. As expected, we found that elimination of I(NaP) shifted the rheobase to more positive currents. More interestingly, elimination of I(NaP) increased the steepness of initial frequency-to-current (fI) relation. This suggests that I(NaP) decreases the transient gain and broadens the integration window for short synaptic inputs in spinal motoneurons.