Involvement of GABAergic and cholinergic medial septal neurons in hippocampal theta rhythm

Abstract

Hippocampal theta rhythm (HPCtheta) may be important for various phenomena, including attention and acquisition of sensory information. Two types of HPCtheta (types I and II) exist based on pharmacological, behavioral, and electrophysiological characteristics. Both types occur during locomotion, whereas only type II (atropine-sensitive) is present under urethane anesthesia. The circuit of HPCtheta synchronization includes the medial septum-diagonal band of Broca (MSDB), with cholinergic and gamma-aminobutyric acid (GABA)ergic neurons comprising the two main projections from MSDB to HPC. The primary aim of the present study was to assess the effects of GABAergic MSDB lesions on urethane- and locomotion-related HPCtheta, and compare these effects to those of cholinergic MSDB lesions. Saline, kainic acid (KA), or 192 IgG-saporin (SAP) was injected into MSDB before recording. KA preferentially destroys GABAergic MSDB neurons, whereas SAP selectively eliminates cholinergic MSDB neurons. A fixed recording electrode was placed in the dentate mid-molecular layer, and stimulating electrodes were placed in the posterior hypothalamus (PH), and medial perforant path (PP). Under urethane anesthesia, HPCtheta was induced by tail pinch, PH stimulation, and systemic physostigmine; none of the rats with KA or SAP showed HPCtheta in any of these conditions. During locomotion, HPCtheta was attenuated, but not eliminated, in rats with KA or SAP lesions. Intraseptal KA in combination with either intraseptal SAP or PP lesions reduced locomotion-related HPCtheta beyond that observed with each lesion alone, virtually eliminating HPCtheta. In contrast, intraseptal SAP combined with PP lesions did not reduce HPCtheta beyond the effect of each lesion alone. We conclude that both GABAergic and cholinergic MSDB neurons are necessary for HPCtheta under urethane, and that each of these septohippocampal projections contributes to HPCtheta during locomotion.

Selective septohippocampal – but not forebrain amygdalar – cholinergic dysfunction in diencephalic amnesia

“…Our results suggest that these neurons are also less sensitive to the neural insults caused by thiamine deficiency. Our population estimates of ChAT immunopositive cells in the NBM, and the MS/DB, are similar to other published results using stereological estimation techniques [35,56]. It should be pointed out that significantly lower number of ChAT immunopositive cells does not necessarily indicate cell death, although it is commonly used as a measure of cholinergic cell loss [34,56].…”

“…This lack of adaptation in the hippocampal cholinergic response may be due to the loss of MS/DB cells in the PTD model. There is evidence that both cholinergic and GABAergic cells in the MS/DB modulate neural activation of the hippocampus [1,56,60]. Cholinergic activation in the hippocampus triggers rhythmic activity that can persist for hours and such rhythmic activity is related to both learning and neural plasticity [11].…”

Vestibular stimulation enhances hippocampal long-term potentiation via activation of cholinergic septohippocampal cells

“…We showed here that cholinergic activation during a rotation-induced theta rhythm is required for the enhancement of LTP. GABAergic and glutamatergic neurons in the MS may participate in generating a theta rhythm [32,[80][81][82], but the participation of these non-cholinergic inputs in hippocampal LTP during rotation and walking has not been shown.…”

“…After systemic cholinergic blockade, LTP facilitation was abolished [26] but theta rhythm remained correlated with voluntary movements [28,29]. Theta power during walking was reduced [30][31][32] or not significantly changed [33] after 192 IgG-saporin lesion of cholinergic septal neurons. These results suggest the existence of a non-cholinergic, atropine-resistant theta during voluntary movements.…”

Selective Manipulation of Neural Circuits

“…Saporin kills cells by inactivating ribosomes thereby inhibiting translation [169]. Targeting specific cell types and circuits has been accomplished with local injection of modified saporins that is conjugated with various proteins including cell type-specific antibodies and the neurotransmitter substance P [170][171][172][173][174][175][176][177]. Some neurotoxins, such as tetanus toxin and botulinum toxin are retrogradely transported by presynaptic neurons.…”