Also observed was purchase Bay 43-9006 a reduced impact on low-frequency (<10 Hz) power as compared to fixed and jittered stimulation pulses. Cross-frequency stimulation Cross-frequency

interactions, such as those between theta and gamma frequencies, are thought to play an important role in neural processing, such as perception and memory (Jensen and Colgin, 2007). In order to try and artificially generate a theta–gamma coupled state, we stimulated the MS at 50 mW/mm2 with four 10 ms pulses at 42 Hz with the cycle occurring at a frequency of 7 Hz (Figure ​Figure7G7G). This produced a highly sinusoidal pattern in the LFP, as demonstrated by the peristimulus average (Figure ​Figure7H7H) and consistent with what has been observed previously (Figure ​Figure33). Spectral analysis demonstrated a complex response dominated by power bands at 7 and 42 Hz (Figure ​Figure7I7I). Harmonics of the 7 Hz response were visible, but the amplitude varied considerably and in a pattern unlike that previously encountered (Figures ​Figures44 and ​55). It is likely that constructive and destructive interference between the harmonics of the 7 and 42 Hz components of the response are responsible for the particular patterning observed. Continuous sinusoidal Continuous optical stimuli, as opposed to pulsed stimuli, can introduce stimulus currents that

better mimic natural synaptic bombardment (Tchumatchenko et al., 2013). Therefore, we also explored stimulating with a continuous 23 Hz sinusoidal signal (Figure ​Figure7J7J). The average response was more sinusoidal than fixed frequency (Figure ​Figure7K7K). As in other stimulation cases, power was largely concentrated at the stimulus frequency as well, with a reduced harmonic component as compared

to the fixed-frequency pulses (Figure ​Figure7L7L). Intriguingly, this stimulation pattern seemed to alter the LFP at frequencies other than just the stimulation frequency, with stimulation onset correlating with a consolidation of power at theta frequencies into two discrete bands as calculated across several trials. VALIDATION OF HIPPOCAMPAL RESPONSE TO PULSATILE STIMULATION PATTERNS IN THE HIPPOCAMPUS In our second example experiment, we explored stimulation and recording from the same site, namely, the dorsal hippocampus (Figure ​Figure2B2B). NeuroRighter is compatible with Drug_discovery a wide variety of electrode configurations, as evidenced in our use of the combined NeuroNexus array and optical ferrule in this example (Figure ​Figure1J1J). Optically stimulating and electrically recording in the same location does possess a significant caveat, in the form of optically induced artifacts on the recording electrodes (Ayling et al., 2009; Han et al., 2009; Cardin et al., 2010) that must be separated from the true neurologic signal.