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Pikus, M.

Publications and source records attributed to Pikus, M..

4 recordsLinked to original sources

Spike-wave discharges reflect widespread, but non-uniform, cortical hypersynchrony during immobility

Spike-wave discharges (SWDs) are the electrographic hallmark of absence epilepsy, yet direct evidence for their proposed basis in cortical hypersynchrony has been scarce. We addressed this gap by recording neuronal populations across three cortical regions - primary somatosensory (S1), visual (V1), and secondary motor cortex (M2) - using silicon probe arrays in spontaneously seizing C3H/HeJ mice. SWDs drove profound increases in neuronal synchrony, rhythmicity, and phase-locking across all recorded regions. V1 and M2 neurons were clearly entrained to SWD cycles, though less strongly than S1 neurons. Electrical stimulation of both S1 and V1 could induce or terminate SWDs, supporting widespread network involvement. Finally, we also provide evidence that SWD-associated reductions in firing rate could be attributable to co-occurring behavioral immobility rather than to the seizures themselves.

neuroscience↗

Thalamic hubs as early sources of global neuronal synchrony in absence epilepsy

Generalized seizures reflect a pathological state of sudden, global neuronal hypersynchrony. The mechanisms that support the initiation and maintenance of such synchrony remain unknown. Using simultaneous single-unit and electrocorticographic recordings in two mouse models of absence epilepsy, we evaluated the activity of approximately 2,000 individual neurons across 26 brain structures. By doing so, we resolved the temporal progression of single neuron activity prior to and during generalized seizures. Surprisingly, we observed that rhythmic, synchronized activity emerges early and gradually in both thalamus and cortex. Moreover, while we observe that individual neurons across most structures fire rhythmically and synchronously during seizures, a small subset of midline thalamic nuclei display activity that is strongly correlated across multiple regions. Finally, disturbing neuronal activity within the midline thalamus terminates seizures. Thus, our findings collectively highlight the possible role of the midline thalamus in emergence of neuronal hypersynchrony.

neuroscience↗

Behavioral and neural correlates of diverse conditioned fear responses in male and female rats

Pavlovian fear conditioning is a widely used tool that models associative learning in rodents. For decades the field has used predominantly male rodents and focused on a sole conditioned fear response: freezing. However, recent work from our lab and others has identified darting as a female-biased conditioned response, characterized by an escape-like movement across a fear conditioning chamber. It is also accompanied by a behavioral phenotype: Darters reliably show decreased freezing compared to Non-darters and males and reach higher velocities in response to the foot shock ("shock response"). However, the relationship between shock response and conditioned darting is not known. This study investigated if this link is due to differences in general processing of aversive stimuli between Darters, Non-darters and males. Across a variety of modalities, including corticosterone measures, the acoustic startle test, and sensitivity to thermal pain, Darters were found not to be more reactive or sensitive to aversive stimuli, and, in some cases, they appear less reactive to Non-darters and males. Analyses of cFos activity in regions involved in pain and fear processing following fear conditioning identified discrete patterns of expression among Darters, Non-darters, and males exposed to low and high intensity foot shocks. The results from these studies further our understanding of the differences between Darters, Non-darters and males and highlight the importance of studying individual differences in fear conditioning as indicators of fear state.

neuroscience↗

Sounding the alarm: sex differences in rat ultrasonic vocalizations during Pavlovian fear conditioning and extinction

Pavlovian fear conditioning is a prevalent tool in the study of aversive learning, which is a key component of stress-related psychiatric disorders. Adult rats can exhibit various threat-related behaviors, including freezing, motor responses and ultrasonic vocalizations (USVs). While these responses can all signal aversion, we know little about how they relate to one another. Here we characterize USVs emitted by male and female rats during cued fear acquisition and extinction and assess the relationship between different threat-related behaviors. To probe the effects of aversive stimulus intensity, we exposed the rats to mild (0.3 mA), moderate (0.5 mA) or strong (1 mA) foot shocks. We found that males consistently emitted more alarm calls than females, and male alarm calls were more closely contingent on shock intensity than were female alarm calls. Furthermore, 25 % of males and 45 % of females did not emit alarm calls. Males that made alarm calls had significantly higher levels of freezing than males who did not, while no differences in freezing were observed between female alarm callers and non-callers. Alarm call emission was also affected by the predictability of the shock; when unpaired from a tone cue, both males and females started emitting alarm calls significantly later. Some rats continued to alarm-call during extinction learning (90% of males, 30% of females) and retrieval (65% of males, 20% of females). Collectively these data suggest sex-dependence in how behavioral readouts relate to innate and conditioned threat responses. Importantly, we suggest that the same behaviors can signal sex-dependent features of aversion. Significance statementBehavioral neuroscientists can access various outputs during behavioral tests to draw conclusions about internal states of animals. While freezing is the most common index of rodents feeling threatened, these animals also emit specific ultrasonic vocalizations during aversive situations. Here we record several motor and vocal behaviors to assess how they relate to each other as threat responses, and how such relationships vary across sex. We found robust differences in how much male and female rats engaged in so-called alarm vocalizations. These vocalizations were subject to extinction in both sexes, but correlated with freezing only in males. As the field advances to include more females in preclinical research, it is crucial that we understand how similar-appearing outputs may reflect sex-biased features.

animal behavior and cognition↗