Hippocampal CA3 and CA2 have distinct bilateral innervation patterns to CA1 in rodents

Ipsi-and contralateral hippocampal CA3–CA1 and CA2–CA1 projections were investigated in adult male Long–Evans rats by retrograde tracing. Injection of the retrograde tracer cholera toxin subunit B in the strata oriens and radiatum of dorsal CA1 resulted in labeling of predominantly pyramidal cells in ipsilateral and contralateral CA3 and CA2. The contralateral and ipsilateral anterior–posterior extents of CA3 innervation to CA1 were similar. Fifteen to twenty per cent of the hippocampus proper cells that give rise to CA1 stratum oriens innervation were CA2 pyramidal cells, whereas CA2 cells were a mere 3% for CA1 stratum radiatum innervation. The preferred projection of CA2 pyramidal cells to the CA1 stratum oriens was also manifested in transgenic mice that express GFP under the control of the CACNG5 promoter, in which CA2 cells express high amounts of GFP. The ratios of ipsilateral to contralateral projections were compared. For the CA3–CA1 connection, we found that dorsal CA1 stratum radiatum received more ipsilateral projections whereas CA1 stratum oriens received more contralateral innervation. Interestingly, ipsilateral connections dominated for both CA2–CA1 stratum oriens and CA2–CA1 stratum radiatum. These results demonstrate that the primary intrahippocampal target of CA2 pyramidal cells is the ipsilateral CA1 stratum oriens, in contrast to CA3 cells which project more diversely to bilateral CA1 regions. Such innervation patterns may suggest differential dendritic information processing in apical and basal dendrites of CA1 pyramidal cells.textapplication/pdfjournal articl

Electrical and chemical modulation of Adult Hippocampal Neurogenesis

Dissertation. Ph.D. American University of Beirut. Department of Anatomy, Cell Biology and Physiological Sciences. Faculty of Medicine 2018. W 4 C442e 2018; Chairman: Nayef E. Saadé, DSc, Chairman, Professor Department of Anatomy, Cell Biology and Physiological Sciences ; Advisor: Wassim Abou-Kheir, PhD, Associate Professor, Department of Anatomy, Cell Biology and Physiological Sciences ; Co-Advisor: Elie D. Al-Chaer, PhD, JD, Professor, Department of Anatomy, Cell Biology and Physiological Sciences ; Committee members: Samir Atweh, MD, Professor, Department of Neurology ; Ziad Nahas, MD, Professor, Department of Psychiatry ; Huda Huijer, RN, PhD, FEANS, FAAN, Professor, Hariri School of Nursing ; Bared Safieh-Garabedian, PhD, Professor, Faculty of Medicine, Qatar University ;Joseph Maarrawi, MD, PhD, Associate Professor, Faculty of Medicine, USJ.Includes bibliographical references (leaves 125-146)Background: Despite the advances in technology that has steered clinical trials to new approaches and surgical modalities, the basic scientific knowledge of how these technologies work is still controversial. Deep brain stimulation (DBS), for example, has developed during the past 20 years, providing substantial clinical benefit for a variety of movement disorders such as Parkinson’s disease, essential tremor and dystonia. It is, however, still unknown how DBS alters neural activity and the neuronal electrophysiology to induce beneficial outcomes. One area of interest is to investigate a possible role for modulation of adult hippocampal neurogenesis in mediating DBS effects. The hippocampus is a structural and functional component of the limbic system and is known to be a neurogenic niche containing neural stem-progenitor cells in the subgranular zone (SGZ) of the dentate gyrus (DG). It possesses extensive interconnections with the anteromedial thalamic nucleus (AMN) proposing that electrical stimulation of the AMN conveys physiological fluctuations to the hippocampus and possibly elicits neurogenesis. The specificity of the electrical signal is dubious, however, and it results in inadvertent stimulation to nearby regions and to the passing fibers. Therefore, a more specific targeting of the AMN cell bodies might be done through chemical stimulation. This is accomplished by using low doses of Kainic acid (KA), a direct agonist of the Glutamic Kainate receptors, to evoke sustained neuronal activation without causing seizures. Objective: The aim of this study is to examine the effect of AMN stimulation in modulating adult hippocampal neurogenesis at early and later stages to follow the fate of stem-progenitor cells proliferation. This study includes single as well as multiple sessions of electrical stimulation of the AMN using two types of electrodes (cupper or platinum) and chemical stimulation or continuous KA micro-perfusion of that nucleus by an implanted mini-osmotic pump. Methods: Adult Sprague-Dawl

Coordinated memory processing between the dorsal and ventral hippocampus and the nucleus accumbens

The brain’s ability to associate experiences with subsequent rewards is fundamental to learning and memory and critical for animal survival. The neural substrates of this process are only partially understood, but are thought to rely on interactions between the hippocampus and nucleus accumbens (NAc). In particular, hippocampal input to the NAc is thought to be crucial for learning and remembering links between spatial information and reward. Hippocampal projections to the NAc arise from both the ventral hippocampus (vH) and the dorsal hippocampus (dH), and studies using optogenetic interventions have demonstrated that either vH or dH input to the NAc can support behaviors dependent on spatial-reward associations. It remains unclear, however, whether dH, vH, or both coordinate memory processing of spatial-reward information in the hippocampal-NAc circuit under normal conditions. Moreover, as dH and vH are thought to encode different aspects of an experience, whether the hippocampus can compartmentalize different types of information to circuits in the NAc is unknown. Times of memory reactivation within and outside the hippocampus are marked by hippocampal sharp-wave ripples (SWRs), discrete events which facilitate investigation of inter-regional information processing. It is unknown whether dH and vH SWRs act in concert or separately to engage NAc neuronal networks, and whether either dH or vH SWRs are preferentially linked to spatial-reward representations. To address these questions, we performed simultaneous extracellular recordings using multi-tetrode arrays in the dH, vH, and NAc of rats learning and performing an appetitive spatial task and during sleep. We report that dH and vH SWRs occur asynchronously, and that individual NAc neurons activated during SWRs from one subdivision of the hippocampus are typically suppressed or unmodulated during SWRs from the other. Furthermore, NAc neurons activated during dH versus vH SWRs show markedly different task-related firing patterns, with NAc representations related to space and reward selectively activated during dH SWRs and not vH SWRs. Our findings reveal that dorsal and ventral hippocampal interactions with the NAc are temporally and anatomically separable at times of memory processing. This work suggests that the dH-NAc and vH-NAc networks provide distinct information channels, with the dH-NAc channel dedicated to linking spatial paths with reward and reward-seeking actions. More broadly, these circuit dynamics could provide a potential neural substrate for the brain’s ability to compartmentalize aspects of experience in memory

Aktivace paměti v neuronových sítích mozku

The processes of association and separation of individual mental representations are essential for normal cognitive functions. They are vital for both non- declarative and declarative memory, especially for semantic memory, episodic memory, symbolic language, imagination and spatial orientation. Distruptions in these phenomena can have profound consequences leading to pathological conditions such as dementia or psychosis. Hippocampus, being the centerpoint of the declarative memory system, offers a valuable window for studying the formation, reactivation and modification of memory traces. Insight into mechanisms of hippocampal spatial coding provides a uniquely transparent view on neural representations, whose dynamical nature is central to processes of thought and cognition in general. Evolutionary preservation of the hippocampus and medial temporal lobe memory system enables us to study building blocks of complex phenomena, such as episodic memory, in simpler animal models. My thesis focuses on the dynamics of awake reactivation of hippocampal place cell population patterns from different environmental contexts. This ability is supposedly a key prerequisite for declarative, conscious recollection we can observe in humans. We discovered that rat models are capable of reactivating neuronal codes...Procesy asociace a separace jednotlivých mentálních reprezentací jsou nezbytné pro normální kognitivní funkce. Důležité jsou pro nedeklarativní i deklarativní paměť, zejména pro sémantickou paměť, epizodickou paměť, symbolický jazyk, představivost i prostorovou orientaci. Narušení těchto jevů může mít dalekosáhlé následky a vést k výskytu takových patologických jevů, jako demence či psychóza. Hipokampus, středobod deklarativního paměťového systému, nabízí cenné okno umožňující studium formování, reaktivace a modifikace paměťových stop. Vhled do mechanismů hipokampálního prostorového kódování poskytuje jedinečně transparentní obraz neurálních reprezentací, jejichž dynamická podstata je zásadní pro procesy myšlení i kognice obecně. Zachování hipokampu a mediálního temporálního paměťového systému napříč evolucí umožňuje studium stavebních kamenů komplexních jevů, jako je například epizodická paměť, i v jednodušších animálních modelech. Má disertační práce se zaměřuje na dynamiku bdělé reaktivace hipokampálních vzorců pozičních buněk v různých prostorových souvislostech. Tato schopnost je považována za klíčovou prerekvizitu pro deklarativní, vědomé vybavování, které můžeme pozorovat u lidí. Objevili jsme, že potkaní modely jsou schopné reaktivovat neurální kódy odpovídající prostředím odlišným od těch,...Ústav patologické fyziologieLékařská fakulta v PlzniFaculty of Medicine in Pilse

Time to put the mammillothalamic pathway into context

The medial diencephalon, in particular the mammillary bodies and anterior thalamic nuclei, has long been linked to memory and amnesia. The mammillary bodies provide a dense input into the anterior thalamic nuclei, via the mammillothalamic tract. Lesions of the mammillary bodies, mammillothalamic tract and anterior thalamic nuclei all produce severe impairments in temporal and contextual memory, in both animal models and in patients, yet it is uncertain why these regions are critical. Mounting evidence from electrophysiological and neural imaging studies suggests that mammillothalamic projections exercise considerable distal influence over thalamo-cortical and hippocampo-cortical interactions. Here, we outline how damage to the mammillary body-anterior thalamic axis, in both patients and animal models, disrupts behavioural performance on tasks that relate to contextual (“where”) and temporal (“when”) processing. Focusing on the medial mammillary nuclei as a possible ‘theta-generator’ (through their interconnections with the ventral tegmental nucleus of Gudden) we discuss how the mammillary body-anterior thalamic pathway may contribute to the mechanisms via which the hippocampus and neocortex encode representations of experience