WHY ARE THERE PARALLEL HIPPOCAMPAL DIENCEPHALIC PATHWAYS FOR

WHY ARE THERE PARALLEL HIPPOCAMPAL - DIENCEPHALIC PATHWAYS FOR EVENT MEMORY? Wellcome Trust Project JOHN AGGLETON SHANE O’MARA JONATHAN ERICHSEN SERALYNNE VANN

Presentation format • • Introduction to synaptic plasticity and memory Hippocampal-diencephalic system (HDS) Mammillary bodies (MB) Anterior thalamic nuclei (ATN) • Lesion studies • Subiculum • Overview

Introduction Synaptic plasticity >> Memory • Different types of: Plasticity memory circuits synaptic plasticity induction Sjöström and Nelson, Curr Op Neurobiol, 2002 plasticity involved cells Sjöström and Nelson, Curr Op Neurobiol 2002 plasticity cellular targets intracellular mechanisms

Introduction Long term synaptic plasticity in hippocampal related circuits >> Episodic memory

Introduction Hippocampus related circuits

Introduction Hippocampus related circuits

Introduction Hippocampus related circuits

HDS Hippocampal - diencephalic system Lesion studies : the hippocampal diencephalic system is required for the encoding of episodic information. Still the functional significance of this system for the memory formation is under construction.

Significance of the parallel thalamic projections (direct and via MB) Hippocampal –diencephalic circuit (Papez’s circuit): hippocampal formation → MB → anterior thalamus → cingulate cortex → parahippocampal gyrus → hippocampal formation MB are part of the extended hippocampal - diencephalic system HDS

HDS Medial & lateral diencephalic systems Rec/Stim

Methodology Methods and approaches • Retrograde markers tracing • Lesion application + Behavioural examination (learning tasks) • IEG activity immunohistochemistry • Field EPSP recording under anaesthesia • Field EPSP + Lesion application under anaesthesia • EEG under anaesthesia and in freely moving rats • Unit recording under anaesthesia and in freely moving rats • Others (f. MRI, microdialysis) • • • PPF LTP LTD STDP Theta

HDS Medial & lateral diencephalic systems

Significance of the parallel thalamic projections (direct and via MB) MB MMB involvement in spatial working memory tasks: - lesion techniques - c-fos protein expression - cytochrome oxidase (CO) aczivity (Conejo et al. , 2004).

MB MB lesions – the mildest outcome Spatial deficits after MB damage are not as severe as those found after hippocampectomy and are typically less severe than those associated with ATN damage. Anatomical or functional bypassing possibility?

MB MMB coordinates - AP: 4. 5 - 5. 2 mm

MB MB function: relayers of hippocampal theta rhythm - to the ATN and beyond • theta-related cells in the MB seem to be driven by descending projections from the hippocampus • and are especially correlated with the CA 1 theta generators.

MB MB function: relayers of hippocampal theta rhythm - to the ATN and beyond • Propolsals about the significance of this relay: • 1. relaying of theta by the mammillary bodies might reduce interference by helping to separate encoding and retrieval (Hasselmo et al. , 2002) • 2. theta activity im parallel with head direction processing facilitates the transmission and plasticity of LMN – AD thalamus - retrosplenial information (Vertes et al. , 2004). • 3. theta oscillations of MMB facilitate the information current in Papez’s circuit

Synaptic plasticity and hippocampo-diencephalic system ATN convergence has a gating effect on theta and its potential to act upon the retrosplenial cortices and back upon the hippocampus. MB

ATN Anterior thalamus and theta • Approximately 75% of ventral ANT cells fire synchrony with hippocampal theta rhythm. • Active locomotion increases peak firing rates of anterodorsal thalamic head direction cells. The level of locomotor activity provides a statedependent modulation of the response magnitude of AD HD cells (Zugaro et al. , 2001).

ATN Anterior thalamus nuclei (ATN)

ATN coordinates

ATN coordinates - AP: 1. 4 mm

Lesion studies Hippocamal – diencephalic plasticity lesion studies

Lesion studies Postcommissural fornix lesions Pilot studies postcommissural fornix lesions.

Lesion studies Mammillothalamic tract lesions Vann and Aggleton, 2003; Vann et al. , 2003: mammillothalamic tract lesions (MTTx) coordinates of the lesion relative to ear-bar zero were AP +4. 2 and L +0. 9, and the depth from top of cortex was +6. 9 mm.

Subiculum – the major challange of the project Subiculum

Subiculum Ventral vs. dorsal subiculum Naber and Witter, 1998

Subiculum Subicular coordinates Transverse sections perpendicular to the long axis of the hippocampal formation (Ishizuka 2001).

Subiculum Subicular AP coordinates: 5. 2 - 5. 6 mm

Overview AP spatial configuration of all electrodes MM: 4. 5 – 5. 2 ATN: 1. 4 – 2. 1 Sub: 5. 2 – 5. 6

Overview Hippocampal - diencephalic plasticity, system approach PLASTICITY IN THE PROJECTION FROM THE ATN TO THE ANTERIOR CINGULATE CORTEX (Gemmell and O‘Mara, 2002)

Overview Regional specific long-term synaptic plasticity Physiological substrate of hippocampal diencephalic plasticity – possible key to the encoding of temporal sequences (episodes).

Overview Hippocampal - diencephalic system: basic approach to the episodic memory

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