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

Synaptic plasticity >> Memory

• Different types of:

memory

memory circuits

plasticity involved cells

synaptic plasticity

plasticity induction

plasticity cellular targets

intracellular mechanisms

Plasticity

Sjöström and Nelson, Curr Op Neurobiol, 2002

Sjöström and Nelson, Curr Op Neurobiol 2002

Introduction

Long term synaptic plasticity in hippocampal related circuits

>> Episodic memory

Introduction

Hippocampus related circuitsIntroduction

Hippocampus related circuitsIntroduction

Hippocampus related circuitsIntroduction

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.

HDS

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

Medial & lateral diencephalic systems

Rec

Stim

Rec/Stim

HDS

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 (fMRI, microdialysis)

• PPF• LTP• LTD• STDP • Theta

Methodology

Medial & lateral diencephalic systemsHDS

Significance of the parallel thalamic projections (direct and via 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 CA1 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

MB

ATN convergence has a gating effect on theta and its potential to act upon the retrosplenial

cortices and back upon the hippocampus.

Synaptic plasticity and hippocampo-diencephalic system

MB

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

ATN coordinatesATN

ATN coordinates - AP: 1.4 mmATN

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.

Lesion studies

Subiculum – the major challange of the project

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 mmSubiculum

AP spatial configuration of all electrodes

MM: 4.5 – 5.2

Sub: 5.2 – 5.6

ATN: 1.4 – 2.1

Overview

PLASTICITY IN THE PROJECTION FROM THE ATN TO THE ANTERIOR CINGULATE CORTEX (Gemmell and O‘Mara, 2002)

Hippocampal - diencephalic plasticity, system approach

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

Overview

Thank you for your attention