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INTRODUCTION: Theta rhythm is one of the brain rhythms’ patterns, which are evidence for neuronal synchrony. This pattern of rhythmic activity is related to sensorimotor integration, mnemonic functions, or spatial orientation and navigation. However, it is also linked to pathological conditions, for instance: Alzheimer’s disease, post‑traumatic stress disorder, and depression. In the last decade, we discovered that the posterior hypothalamic area (PHa) is not only a modulator of brainstem information going to the hippocampus, but also is capable of generating theta rhythm independently. AIM(S): The aim of the present study was to determine if NMDA (N-Methyl-D-aspartic acid) is capable of eliciting well-synchronized theta activity in PHa preparations. METHOD(S): The study was performed on 40 PHa slices prepared from 20 male Wistar rats. Each animal was anesthetized with isoflurane and decapitated. The PHa slices were dissected and transferred into the recording chamber, perfused with artificial cerebrospinal fluid, and treated with NMDA (300 µM) and D-AP5 (D‑(–)‑2‑amino‑5‑phosphonopentanoic acid) (200 µM). The field recordings were performed with glass electrodes filled with 2.0 M sodium acetate. RESULTS: Perfusions of PHa slices with 300 µM NMDA resulted in well-synchronized theta episodes which were blocked after the path application of 200 µM D‑AP5. CONCLUSIONS: The present data shows that excitation of NMDA-type glutamatergic receptors in PHa neural networks leads to the generation of local theta rhythms. FINANCIAL SUPPORT: Supported by NCN grant no. 2017/25/B/NZ4/01476.
INTRODUCTION: Neuronal synchronization depends on many factors including HCN channel action. They are voltage-gated ion channels that mediate an inward cationic current dependent on hyperpolarization. There is sparse evidence for their contribution to neuronal plasticity, learning and memory, epilepsy, or Alzheimer’s disease. HCN channels can be found in the hippocampus (HPC) and are thought to be involved in neuronal synchronization through initiating membrane potential oscillations which are necessary for the appearance of field theta oscillations. Hippocampal theta rhythm is known to be involved in memory formation, spatial navigation, sensorimotor integration, movement initiation, and others. So far it is established that HPC theta generation is a result of a fine balance between the cholinergic and GABAergic system activation, which triggers the synchronous action of theta-related neurons. However, the involvement of HCN channels in this process is still mostly unknown. AIM(S): The aim of this study was to investigate the role of HCN channel activation in the process of theta generation. METHOD(S): Three experimental models were used: in vivo anesthetized rats, in vitro acute HPC slices, and HPC patch clamp whole cell method. Field and single neuron recordings were made from the HPC after perfusion with a non-specific HCN channels agonist – lamotrigine (LTG). RESULTS: When LTG was applied it produced mixed results. In particular, it blocked theta rhythm in vitro but significantly enhanced it in vivo. Patch clamp results have shown that LTG reduced the frequency of spontaneous inhibitory postsynaptic currents but also decreased the excitability and membrane resistance of CA1 neurons. Also, LTG reduced membrane potential theta resonance in most CA1 cells. CONCLUSIONS: HCN channels activation was shown to have an impact on the process of theta rhythm generation in the HPC. Current results are discussed. FINANCIAL SUPPORT: Supported by National Science Centre, grant no. 2017/26/D/NZ4/00159.
INTRODUCTION: Theta rhythm typically occurs during memory processes, REM sleep, and spatial navigation but also in epilepsy, migraines, or even mild Alzheimer’s disease (AD). Recent evidence shows that well-synchronized theta rhythm can successfully be recorded locally from the posterior hypothalamic area (PHa), specifically from the supramammillary nucleus (SuM) and the posterior hypothalamic nuclei (PH). The population of theta-related cells in the PHa were found to be similar types to those found in the hippocampal formation. In addition, a new type of cells has been found in the posterior hypothalamic region and based on its regular firing pattern and possible pacemaker role these cells were termed “timing”. AIM(S): The aim of the present study was to investigate the timing of cell populations in both in vivo and in vitro PHa after theta rhythm induction by kainic acid (KA) application. METHOD(S): Twenty in vivo experiments were performed on 20 urethanized rats and 22 in vitro experiments were performed on 40 PHa slices obtained from 22 rats. Theta rhythm and single unit activity were evoked by intra-PHa microinjection of KA (in vivo) or by bath perfusion of PHa slices with KA-containing artificial cerebrospinal fluid (in vitro). RESULTS: A total number of 123 posterior hypothalamic neurons were recorded during both in vivo and in vitro experiments. Among them, 28 neurons were classified as “timing cells” according to their very regular pattern of discharges in a steady frequency in the theta band (3‑12 Hz). Eight timing cells were recorded in in vivo PHa and 20 timing cells were recorded in PHa slices. CONCLUSIONS: The present data show that glutamatergic stimulation of PHa neuronal network with kainic acid results in the activation of specific subpopulation of neutrons, characterized by regular firing pattern in theta frequency range. The role of PHa “timing cell” activity is discussed regarding hippocampal theta rhythm frequency programing. FINANCIAL SUPPORT: Supported by NCN grant No. 2017/25/B/NZ4/01476.
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