R Bocian

Gap junction modulation of hippocampal formation theta and local cell discharges in anesthetized rats

During the past decade experimental evidence has accumulated demonstrating that the electrical communication between neurons through gap junctions (GJs) is a necessary neural mechanism underlying oscillations and synchrony. Here we extended our earlier observations concerning the involvement of GJs in hippocampal theta production. Using trimethylamine, a GJ opener, we demonstrated a reversible increase in theta amplitude and power and an increase in the duration of theta epochs. This effect was accompanied by a decrease in the percentage of recorded theta‐off cells, an increase in the percentage of recorded theta‐on phasic cells, and an increase in the number of rhythmic cell discharges per theta wave. We suggest that all these findings result from an enhanced level of interneuronal excitation, mediated by an increase in the efficacy of local GJ coupling.

The effect of carbenoxolone on hippocampal formation theta rhythm in rats: in vitro and in vivo approaches.

The role of gap junction (GJ) coupling in the generation of hippocampal formation theta rhythm was investigated in vitro, with use of brain slices, and in vivo, with use of urethane anesthetized rats. Carbenoxolone, the succinyl ester of glycyrrhetinic acid, and GJ blocker reversibly abolished hippocampal formation theta rhythm recorded in slice preparations and urethane anesthetized rats. The present study yielded novel data which demonstrated that the pattern of delay in blockage of theta rhythm after carbenoxolone treatment, and the pattern of theta recovery after administration of this agent, require a specific time period (2-3h for delay and 8-12h for recovery), one that can be demonstrated using different experimental protocols.

The effect of posterior hypothalamic injection of cholinergic agents on hippocampal formation theta in freely moving cat

The effect of intra-hypothalamic micro-injection of muscarinic (atropine sulphate, pirenzepine and gallamine) and nicotinic (hexamethonium) antagonists on spontaneous, sensory and electrically-induced hippocampal formation (HPC) theta EEG activity was investigated in the freely behaving cat. Administration of hexamethonium and gallamine failed to elicit a detectable effect on HPC theta activity. However, the injection of atropine sulphate and pirenzepine abolished the theta rhythm recorded from HPC. This effect was reversible. A substantial difference in the recovery time course between frequency versus amplitude (microV) and power (microV2) of hippocampal theta was observed. While theta frequency exhibited a rapid reappearance with a shallow slope, the power and amplitude showed a gradual recovery with a steeper slope. The injection of carbachol into posterior hypothalamus (PH) produced almost a continuous HPC theta with increased power. These results demonstrate that cholinergic (M1) receptors localised in the posterior area of the hypothalamus are engaged in mechanisms responsible for generating hippocampal theta oscillations in the freely behaving cat. The contribution of posterior hypothalamic region to HPC theta frequency and amplitude is discussed.

The generation of theta rhythm in hippocampal formation maintained in vitro

The most spectacular example of oscillations and synchrony which appear in the brain is the rhythmic slow activity (theta) of the limbic cortex. Theta rhythm is the best synchronized electroencephalographic activity that can be recorded from the mammalian brain. Hippocampal formation is considered to be the main structure involved in the generation of this activity. Although detailed studies of the physiology and pharmacology of theta‐band oscillations have been carried out since the early 1950s, the first demonstration of atropine‐sensitive theta rhythm, recorded in completely deafferented hippocampal slices of a rat, was performed in the second half of the 1980s. Since the discovery of cholinergically induced in vitro theta rhythm recorded from hippocampal formation slices, the central mechanisms underlying theta generation have been successfully studied in in vitro conditions. Most of these experiments were focused on the basic question regarding the similarities between the cholinergically induced theta activity and theta rhythm examined in vivo. The results of numerous in vitro experiments strongly suggest that cholinergically induced theta rhythm recorded in hippocampal slices is a useful analogue of theta observed in intact animals, and could be helpful in searching for the mechanisms of oscillations and synchrony in the central nervous system neuronal networks. The objective of the present review is to discuss the main results of experiments concerning theta oscillations recorded in in vitro conditions. It is our intent to provide, on the basis of these results, the characteristics of essential mechanisms underlying the generation of atropine‐sensitive in vitro theta.

Theta‐related gating cells in hippocampal formation: In vivo and in vitro study

In this study we extended our earlier in vitro findings concerning the discovery of a novel type of theta‐related cells, which we have termed gating cells. There were two main objectives of our present investigations. The first was to determine the distribution of theta gating cells in the separated CA1 and CA3 generators in three different pharmacological conditions: (i) the presence of a cholinergic agonist—carbachol, (ii) the presence of carbachol and GABAAergic antagonist—bicuculline, (iii) the presence of carbachol and GABABergic antagonist—2‐hydroxysaclofen. The second objective of our studies was to verify our earlier in vitro findings and to demonstrate, for the first time, gating cells in intact hippocampus during the generation of Type II theta in urethane anaesthetized rats. Two hundred ninety‐nine theta‐related cells were isolated and recorded from in vivo and in vitro hippocampal formation. Twenty out of all 299 neurons (6.6%) were classified as gating cells. The neuron was classified as a gating cell if it met one of the following criteria: (i) the cell discharges occurred precisely in the beginning and at the end of each theta epoch (gating cell A); (ii) the cell began to discharge just before the transition from non‐theta interval/LIA into the theta epoch (gating cell B); (iii) the cell began to discharge just after the transition from the theta epoch into non‐theta interval/LIA (gating cell C). Our data demonstrates that the appearance of theta epochs and their length, as well as the appearance of non‐theta states (in vivo recorded LIA or in vitro recorded intervals between theta epochs) and their length, may require the existence of a specific population of hippocampal neurons which we termed gating cells.

Atropine-sensitive theta rhythm in the posterior hypothalamic area: in vivo and in vitro studies.

Theta rhythm is the largest, most prominent, and well‐documented electroencephalography activity present in a number of mammals, including humans. Spontaneous theta activity recorded locally in the posterior hypothalamic area (PHa) has never been the subject of detailed studies. The authors have shown that local theta field potentials could be generated in urethane‐anesthetized rats in the supramammillary (SuM) nuclei and posterior hypothalamic (PH) nuclei. Theta recorded in the PHa was produced independently of simultaneously occurring hippocampal theta. These data were confirmed in the PHa maintained in vitro. Local theta field activity was recorded in the SuM and PH nuclei of PHa slice preparations perfused with cholinergic agonist carbachol. Both in vivo and in vitro recorded PHa theta rhythmicity had a cholinergic–muscarinic profile, that is, it was antagonized by muscarinic antagonist atropine sulfate.

Posterior hypothalamic GABAergic mediation of hippocampal theta in the cat.

The effect of posterior hypothalamic (PH) microinjections of GABAA and GABAB agonists (muscimol and baclophen, respectively) and antagonists (bicuculline and 2-OH saclophen) on spontaneous, sensory and electrically induced hippocampal formation (HPC) theta EEG activity was investigated in freely behaving cats. Administration of GABAergic agonists abolished the theta rhythm recorded from HPC. This effect was reversible. A substantial difference in the recovery time course between frequency versus amplitude and power of hippocampal theta was observed. While theta frequency exhibited a rapid reappearance with a shallow slope, the power and amplitude showed a gradual recovery with a steeper slope. The PH injection of GABAergic antagonists produced HPC theta with increased power. These results demonstrate that both types of GABAergic receptors localized in PH are engaged in mechanisms responsible for generating hippocampal theta oscillations in freely behaving cats. The present study provides additional support for the essential difference between rats and cats in the programming of HPC theta amplitude and frequency. While the PH in rats is involved in programming the frequency of theta rhythm, the same region in cats mainly determines theta amplitude.

Orexinergic theta rhythm in the rat hippocampal formation: In vitro and in vivo findings

Previous in vivo data suggested that orexin neuropeptides (ORXA and ORXB) synthetized in hypothalamic neurons were involved in the mechanism of generation of the hippocampal formation theta rhythm. Surprisingly, this suggestion has never been directly proved by experiments using intraseptal or intrahippocampal administration of orexins. In this study, involving the use of in vitro hippocampal formation slices and in vivo model of anesthetized rat, we provide the first convergent electropharmacological evidence that in the presence of both ORXA and ORXB the hippocampal formation neuronal network is capable of producing oscillations in the theta band. This effect of orexin peptides was antagonized by selective blockers of orexin receptors (OX1R and OX2R), SB 334867 and TCS OX2 29, respectively. These results provide evidence for a novel, orexinergic mechanism responsible for the production of theta rhythm in the hippocampal formation neuronal network.

The electrical coupling and the hippocampal formation theta rhythm in rats

Gap junctions (GJs) were discovered more than five decades ago, and since that time enormous strides have been made in understanding their structure and function. Despite the voluminous literature concerning the function of GJs, the involvement of these membrane structures in the central mechanisms underlying oscillations and synchrony in the neuronal network is still a matter of intensive debate. This review summarizes what is known concerning the involvement of GJs as electrical synapses in mechanisms underlying the generation of theta band oscillations. The first part of the chapter discusses the role of GJs in mechanisms of oscillations and synchrony. Following this, in vitro, ex vivo, and in vivo experiments concerning the involvement of GJs in the generation of hippocampal formation theta in rats are reviewed.

Vagus nerve stimulation produces a hippocampal formation theta rhythm in anesthetized rats

Vagus nerve stimulation (VNS) has been used for years to treat patients with drug-resistant epilepsy. In the present study, the effect of different stimulation protocols of VNS on the hippocampal formation (HPC) type II theta field potentials were evaluated in anesthetized rats. The following theta parameters were analysed: power, frequency and duration of theta epochs. We documented for the first time the presence of HPC type II theta in response to the application of VNS. A VNS-induced theta rhythm appeared in different experimental protocols and, depending on the current intensity, could occur directly during VNS (brief effect) or after vagal stimulation (delayed effect), using lower intensity stimuli.