GABA_B receptor blockade enhances theta and gamma rhythms in the hippocampus of behaving rats

Abstract

The participation of GABA(B) receptors in hippocampal EEG generation was studied by intracerebroventricular (icv) and intracerebral infusions of GABA(B) receptor antagonist p-(3-aminopropyl)-p-diethoxymethyl-phosphinic acid (CGP35348) in freely behaving rats. During awake-immobility, icv CGP35348 induced a theta rhythm and increased gamma waves (30-100 Hz) in the hippocampus. The immobility theta peaked at 6-7 Hz and had a theta phase in CA1 stratum radiatum of approximately 160 degrees with reference to the theta at the alveus, when compared with approximately 130 degrees during walking. Immobility theta power peaks at 6-7 Hz was also found in normal rats, and it was detected in 27% of the EEG segments during immobility. Incidence of immobility theta increased to 87.5% after 480 nmol of CGP35348 icv. Muscarinic antagonist scopolamine (5 mg/kg, ip) suppressed the induction of immobility theta and the gamma power increase after icv CGP35348. CGP35348 icv did not significantly change the hippocampal theta power at 7-8 Hz during walking (theta fundamental), but it increased power at 12-15 Hz, at the second harmonic of theta. CGP35348 icv also increased 30-50 Hz gamma power during walking. Medial septal infusion of CGP35348 (12 nmol in 0.4 microl) increased the power and the frequency of the hippocampal theta second harmonic during walking, but did not increase gamma activity. Infusion of CGP35348 (8 nmol in 0.4 microl) in the hippocampus increased the local gamma activity at 30-100 Hz, but did not induce immobility theta or affect the walking theta rhythm. In conclusion, icv GABA(B) receptor blockade increased an atropine-sensitive input that generated an immobility theta rhythm, while GABA(B) receptor blockade of the medial septum increased atropine-resistant theta harmonics possibly generated by apical dendritic spikes. GABA(B) receptor blockade may enhance cognitive task performance by activating hippocampal theta and gamma rhythms in behaving rats.

Suppression of γ-Oscillations in the Dorsolateral Prefrontal Cortex following Long Interval Cortical Inhibition: A TMS–EEG Study

“…For example, animal studies have shown that administration of GABA B receptor agonists such as baclofen eliminates g-oscillations in rat hippocampal slices , whereas the blockade of GABA B receptors has been shown to enhance the g-oscillations in the hippocampus of behaving rats (Leung and Shen, 2007). Consistent with these studies, the stimulus-induced attenuation of g-oscillations was enhanced following the injection of tiagabine .…”

Disinhibition reduces extracellular glutamine and elevates extracellular glutamate in rat hippocampus in vivo

“…CGP concentrations of 0.1 to 1 mM used in this study were based on previous reports that (a) intrahippocampal infusion of 20 - 30 μM CGP permitted study of the effect of GABA B R blockade on theta and gamma rhythms in freely behaving rats (Leung and Shen, 2007), and (b) perfusion of 0.3 - 1 mM CGP in Mg 2+ -free medium evoked increases of extracellular guanosine 3′,5′-cyclic monophosphate (cGMP) without causing behavioral seizures (Fedele et al, 1997). The present study is the first in vivo demonstration that perfusion of 0.1 mM CGP in the hippocampal CA3/CA1 region is sufficient to block the presynaptic GABA B(1a,2) heteroreceptor resulting in GLU ECF elevation (Fig.…”

Theta-Band Phase Locking of Orbitofrontal Neurons during Reward Expectancy

“…Future experiments may test the causal role of OFC theta oscillatory activity in the acquisition and reversal of learned associations, for instance by local infusions of substances that were shown to alter oscillations in other brain structures [e.g., GABA B and muscarinic receptor antagonists (Leung and Shen, 2007) as well as blockers of I h (Glasgow and Chapman, 2008)]. Second, further experiments may examine whether information on negative outcome predictions is also temporally structured by way of oscillatory activity, and how positive predictions about noningestible rewards are coded.…”