Distribution and mRNA Expression of nAChRs in the Rat S1 and M1 Cortices After Electrical Stimulation of the Basal Forebrain.

AIM: To study the changes in the distribution of and the transcriptional levels associated with α4- and α7-subtype nicotinic acetylcholine receptors (nAChRs) in the primary somatosensory (S1) and motor (M1) cortices of rats after electrical stimulation of the basal forebrain (BF). MATERIAL AND METHODS: Immunofluorescence (IF) analyses were performed on brain sections from 20 rats (experimental groups: controls, contralateral, and ipsilateral to BF stimulation). The nAChR receptor complexes were labeled with antibodies and counted (N) in the cortical layers of the hindlimb representation (S1HL), barrel field (S1BF), and M1. To determine the relative transcriptional mRNA levels, qRT-PCR was performed with tissue from the associated brain regions of 14 different animals in two groups, controls and BF stimulation. RESULTS: For all three tested brain regions, N and D (density) of the α7-subtype nAChR increased in both ipsilateral and contralateral hemispheres after BF stimulation. There was no change in N and D of the α4 subtype. Regardless of BF stimulation, N of both subtypes was lower in M1 compared to S1HL and S1BF, and D was highest in layers II-IV. BF stimulation had no significant effect on the relative mRNA levels of both receptor subtypes. CONCLUSION: The results show an upregulation of the α7-subtype nAChR as a result of BF stimulation, based on receptor-complex counts on IF images. However, this change was not reflected in mRNA levels, which suggest post-translational modifications. Overall, this study suggests structural changes from the effects of cholinergic projections to the somatosensory and motor cortices.

Effects of basal forebrain stimulation on the vibrotactile responses of neurons from the hindpaw representation in the rat SI cortex.

Basal forebrain (BF) cholinergic system is important for attention and modulates sensory processing. We focused on the hindpaw representation in rat primary somatosensory cortex (S1), which receives inputs related to mechanoreceptors identical to those in human glabrous skin. Spike data were recorded from S1 tactile neurons (n = 87) with (ON condition: 0.5-ms bipolar current pulses at 100 Hz; amplitude 50 µA, duration 0.5 s at each trial) and without (OFF condition) electrical stimulation of BF in anesthetized rats. We expected that prior activation of BF would induce changes in the vibrotactile responses of neurons during sinusoidal (5, 40, and 250 Hz) mechanical stimulation of the glabrous skin. The experiment consisted of sequential OFF-ON conditions in two-time blocks separated by 30 min to test possible remaining effects. Average firing rates (AFRs) and vector strengths of spike phases (VS) were analyzed for different neuron types [regular spiking (RS) and fast spiking (FS)] in different cortical layers (III-VI). Immediate effect of BF activation was only significant by increasing synchronization to 5-Hz vibrotactile stimulus within the second block. Regardless of frequency, ON-OFF paired VS differences were significantly higher in the second block compared to the first, more prominent for RS neurons, and in general for neurons in layers III and VI. No such effects could be found on AFRs. The results suggest that cholinergic activation induces some changes in the hindpaw area, enabling relatively higher increases in synchronization to vibrotactile inputs with subsequent BF modulation. In addition, this modulation depends on neuron type and layer, which may be related to detailed projection pattern from BF.

Non-NMDA receptor-mediated vibrotactile responses of neurons from the hindpaw representation in the rat SI cortex.

Non-NMDA receptor-mediated vibrotactile responses of neurons from the hindpaw representation were investigated in the rat SI cortex. We recorded single-unit spikes evoked by sinusoidal (duration: 500 ms; frequency: 5, 40, and 250 Hz; amplitude: 100 µm peak-to-peak) stimulation of the glabrous skin. The responses were obtained with microinjection of aCSF (sham), bicuculline, and AMPA near the isolated neurons in anaesthetized rats. Blocking most of the NMDA receptors by ketamine revealed local dynamics differentially modulated by each drug. The responses were generally suppressed after the initial 100-ms period of the 40- and 250-Hz stimulus, but not at 5 Hz. Both drugs increased average firing rates (AFRs) only during vibrotactile stimulation, and increased entrainment as measured by the vector strength (VS) of spike phases. However, bicuculline was more effective on the AFR in the late period particularly at 40 Hz. Complex interactions were found with AMPA; late activity increased only for fast spiking neurons at 40 Hz, and more for regular spiking neurons at 5 Hz. The increase of VS by bicuculline was much higher in layer IV. In addition to thalamocortical feed-forward inhibition, vibrotactile information seems to be suppressed after 100 ms by longer-latency inhibitory networks tuned to mid-frequency inputs. Combined with the presumed AMPA-receptor desensitization, those two inhibitory factors could limit the excitatory flow mostly to lower frequencies. The frequency dependence of the drug effects highlights the role of local cortical dynamics in the hindpaw area.