Recognition memory is our ability to discriminate between new and familiar stimuli and is essential for us to lead normal everyday lives. Such memory requires encoding of information about new and familiar objects, the locations where we saw them, and the formation of robust object-location associations for subsequent memory retrieval. Associative recognition memory depends on distinct but highly interconnected brain regions within the medial temporal lobe, frontal cortex and thalamus. But which regions communicate, and when does communication occur, to form memory associations? Are the same regional connections that are necessary for encoding also required for memory retrieval? Which neuronal and which synaptic mechanisms control encoding and which control retrieval?

We are answering these questions using temporally-precise, pathway-specific silencing, neuronal recordings and interrogation of synaptic mechanisms across the circuits. Activity-driven Cre-inducible gene expression is used to determine specifically the neuronal ensembles in different brain regions and their connections that are critical for encoding and retrieval of associative memory while ex vivo electrophysiology reveals the synaptic mechanisms that control neuronal ensembles activated by learning.

This work will establish how highly dynamic, synaptically connected neuronal populations enable associative recognition memory formation through local and long-range neural networks.

Current Projects

What role do different interneurons in medial prefrontal cortex play in associative recognition memory?

Interneurons in mPFC are essential for controlling local circuit dynamics, but the contributions of mPFC inhibitory interneurons to
associative recognition memory are not known.
Specifically, we will investigate how different interneuron subclasses in mPFC bring about encoding and retrieval of associative recognition memory.
We will achieve this aim through completing the following objectives:
1. Determine the roles of mPFC parvalbumin (PV), somatostatin (SOM) and neuron-derived neurotrophic factor positive
(NDNF) interneurons in the encoding and retrieval phases of object in place associative recognition memory.
2. Hippocampus (HPC), nucleus reuniens (NRe) and medial dorsal thalamus (MD) connections to mPFC have different
roles in the encoding and retrieval of associative memory. We will therefore determine whether PV, SOM and NDNF
interneurons in mPFC receive synaptic inputs differentially from HPC, NRe or MD.
3. Determine if synaptic transmission and plasticity at inputs from HPC, NRe and MD onto PV, SOM and NDNF
interneurons are differentially regulated.
The above objectives will be achieved by a combination of methods including in vivo behaviour, viral transduction of
inhibitory or excitatory opsins to allow selective inhibition/excitation, anatomical tagging of synapses, confocal microscopy,
and in vitro electrophysiology.
Together, the expected outcomes will provide a detailed mechanistic understanding of how different interneuron subtypes
within mPFC, driven by inputs from HPC, NRe and MD, contribute to the encoding and retrieval of associative recognition
memory.

 

Acetylcholine and cerebellar dependent motor learning

The brainstem pedunculopontine nucleus (PPN) is the primary source of cerebellar acetylcholine (ACh). ACh plays a key role in motor learning but the mechanisms by which it controls cerebellar-dependent motor learning are unknown. We will test the hypothesis that PPN cholinergic projections to the cerebellum regulate neuronal function to control the encoding and consolidation of motor learning.

We are using a combination of systems level (in vivo) and brain slice (in vitro) approaches in rats to address the following objectives:

To determine the patterns of neural activity between the PPN and the cerebellum during encoding and consolidation of motor learning.

To determine the cellular mechanisms by which endogenous ACh released from terminals of PPN neurons alters intrinsic properties, synaptic transmission and plasticity in the cerebellum.

To determine the roles of different ACh receptor subtypes in encoding and consolidation of cerebellar motor learning.

 

Roles of dentate gyrus mossy cells in pattern separation/completion

The discrimination of similar episodes and places and their representation as distinct memories depend on a process called pattern separation that is performed by the circuitry of the hippocampal dentate gyrus (hDG). Excitatory hilar mossy cells (MCs) support pattern separation through their connections with different inhibitory interneuron (INT) populations that provide feedback inhibition to granule cells (GCs). In this study, we are investigating how MCs and their synaptic connections with cholecystokinin-expressing interneurons (CCKIs) and parvalbumin-expressing interneurons (PVIs) influence the dynamics of hDG circuitry by using pharmacological agents to reduce neurotransmission from MCs or different INTs, genetically modified (GM) mice to selectively remove MCs from hDG circuitry and optogenetics to manipulate INT activity during GC whole cell/field recordings.