The 40 Hz auditory steady state response (ASSR) is an EEG response of local neural synchrony that is evoked by the repeated presentation of a 40 Hz click train. While the principal cortical generators of this response appear to be the bilateral primary auditory cortices as they show the largest phase locking and evoked power, other regions across the cortical mantle synchronize too, including the prefrontal cortex (PFC) that receives input from the primary auditory cortex and is involved in higher order cognitive functions. In schizophrenia, it is hypothesized that NMDA-mediated disruption in PFC function contributes to cognitive deficits including working memory and executive function. In rodents, NMDA antagonists reliably disrupt set shifting, a working memory task linked to PFC function. It is however not known if NMDA antagonism would disrupt the 40 Hz ASSR in PFC. In the following study, we equipped a group of female SD rats with epidural electrodes targeting the PFC (2.5 mm anterior and 0.8 mm lateral to bregma) and the primary auditory cortex (4.5 mm caudal, 7.5 mm lateral and 3.5 mm ventral to bregma). Two epidural screw electrodes on cerebellum served as ground and reference. After recovery from surgery and acclimation, rats were pretreated with small to modest doses of the NMDA antagonist MK801 (0.025, 0.05 and 0.1 mpk) or saline (1 ml/kg, sc) in a cross-over design, tethered to EEG cables and the EEG signal was amplified and acquired (Signal 7.0; CED1401 Micro 3). Trains of square waves (~ 1 ms duration; 40/s) were generated and played through the house speakers at ~ 65 dB SPL. EEG was acquired as 4 s sweeps while the click train played between 1-2 s of each sweep; 75 trials were recorded from each subject. Sixty minutes after vehicle treatment, robust EEG entrainment was noted in both the temporal cortex as well as the PFC. As expected, the EEG signal power from the temporal cortex was notably larger compared to the PFC. Nevertheless, both regions showed clear 40 Hz entrainment to click trains. However, MK801 effect on the 40 Hz ASSR was disparate across the two regions. In the prefrontal cortex, the intertrial coherence (ITC) of the 40 Hz ASSR was strongly disrupted by MK801 at all doses (P<0.001; Dunnett’s test). Evoked power was significantly reduced only at the highest dose (P<0.0001). In primary auditory cortex, relative to vehicle treatment, evoked power showed a significant increase after 0.025 mpk and 0.05 mpk dose but declined significantly after the 0.1 mpk dose (P<0.05). However, ITC was unaffected (P>0.05). These results indicate that gamma neural synchrony in the PFC is more vulnerable to NMDA antagonist- mediated disruption, as compared to the primary auditory cortex. Moreover, it suggests that executive and cognitive functions may be more readily compromised by NMDA-mediated transmission disturbance even as auditory processing is enhanced or unaffected.
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:asrf-2058 |
| Date | 25 April 2023 |
| Creators | Gautam, Deepshila, Allen, Braden Philip, Berger, Robert Patrick, Simmons, Deberrian R, Brillhart, Wesley, Digavalli, Sivarao V. |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Detected Language | English |
| Type | text |
| Source | Appalachian Student Research Forum |
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