Are the Dorsal and Ventral Hippocampus Functionally Distinct Structures

Regional dissociations within the hippocampus--memory and anxiety.

The learning and remembering of fearful events depends on the integrity of the amygdala, but how are fear memories represented in the activity of amygdala neurons? Here, we review recent electrophysiological studies indicating that neurons in the lateral amygdala encode aversive memories during the acquisition and extinction of Pavlovian fear conditioning. Studies that combine unit recording with brain lesions and pharmacological inactivation provide evidence that the lateral amygdala is a crucial locus of fear memory. Extinction of fear memory reduces associative plasticity in the lateral amygdala and involves the hippocampus and prefrontal cortex. Understanding the signalling of aversive memory by amygdala neurons opens new avenues for research into the neural systems that support fear behaviour.

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Neuronal signalling of fear memory.

Sharp wave ripples (SPW-Rs) represent the most synchronous population pattern in the mammalian brain. Their excitatory output affects a wide area of the cortex and several subcortical nuclei. SPW-Rs occur during "off-line" states of the brain, associated with consummatory behaviors and non-REM sleep, and are influenced by numerous neurotransmitters and neuromodulators. They arise from the excitatory recurrent system of the CA3 region and the SPW-induced excitation brings about a fast network oscillation (ripple) in CA1. The spike content of SPW-Rs is temporally and spatially coordinated by a consortium of interneurons to replay fragments of waking neuronal sequences in a compressed format. SPW-Rs assist in transferring this compressed hippocampal representation to distributed circuits to support memory consolidation; selective disruption of SPW-Rs interferes with memory. Recently acquired and pre-existing information are combined during SPW-R replay to influence decisions, plan actions and, potentially, allow for creative thoughts. In addition to the widely studied contribution to memory, SPW-Rs may also affect endocrine function via activation of hypothalamic circuits. Alteration of the physiological mechanisms supporting SPW-Rs leads to their pathological conversion, "p-ripples," which are a marker of epileptogenic tissue and can be observed in rodent models of schizophrenia and Alzheimer's Disease. Mechanisms for SPW-R genesis and function are discussed in this review.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/hipo.22488

Hippocampal sharp wave‐ripple: A cognitive biomarker for episodic memory and planning

NMDA receptors mediate excitatory postsynaptic potentials throughout the brain but, paradoxically, NMDA receptor antagonists produce cortical excitation in humans and behaving rodents. To elucidate a mechanism for these diverging effects, we examined the effect of use-dependent inhibition of NMDA receptors on the spontaneous activity of putative GABA interneurons and pyramidal neurons in the prefrontal cortex of awake rats. We find that inhibition of NMDA receptors predominately decreases the activity of putative GABA interneurons but, at a delayed rate, increases the firing rate of the majority of pyramidal neurons. Thus, NMDA receptors preferentially drive the activity of cortical inhibitory interneurons suggesting that NMDA receptor inhibition causes cortical excitation by disinhibition of pyramidal neurons. These findings support the hypothesis that NMDA receptor hypofunction, which has been implicated in the pathophysiology of schizophrenia, diminishes the inhibitory control of PFC output neurons. Reducing this effect may be critical for treatment of schizophrenia.

https://www.jneurosci.org/content/jneuro/27/43/11496.full.pdf

NMDA Receptor Hypofunction Produces Opposite Effects on Prefrontal Cortex Interneurons and Pyramidal Neurons

The hippocampus, the prefrontal cortex, and interconnected neural circuits are implicated in several aspects of cognitive and memory processes. The present review is dedicated to the description of the anatomo-functional characteristics of the hippocampo-prefrontal pathway and related neuronal circuits in the rat. This pathway, which originates from the hippocampal CA1/subiculum fields, innervates the prelimbic/medial orbital areas of the prefrontal cortex (PL/MO). Its synaptic influence on cortical pyramidal neurons consists in an early monosynaptic excitation followed by an inhibition and, in some cases, a late excitation. These later effects are likely due to the subsequent activation of the local cortical network. PL/MO areas and the CA1/subiculum both send projections to the nucleus accumbens, a region of the ventral striatum which is particularly implicated in goal-directed behavior. Therefore, emphasis is placed on respective projections from PL/MO areas and from the CA1/subiculum on the "core" and the "shell" regions of the nucleus accumbens, as well as on their interconnected circuits. Signals which are directed to the prefrontal cortex through these circuits might modulate hippocampo-prefrontal inputs. Finally, the direct and/or indirect relationships of the hippocampus, prefrontal cortex, and nucleus accumbens with the ventral tegmental area/substantia nigra pars compacta complex (VTA/SNC) (where dopamine neurons are located) will also be described, because these neurons are known to modulate synaptic transmission and plasticity in their target structures and to play a fundamental role in motivational processes.

Hippocampo-prefrontal cortex pathway: anatomical and electrophysiological characteristics.

The hippocampus and prefrontal cortex (PFC), two structures implicated in learning and memory processes, are linked by a direct hippocampo-prefrontal pathway. It has been shown that PFC pyramidal cells receive monosynaptic excitatory inputs from the hippocampus and, in this study, we sought to determine the influence of the hippocampus on PFC interneurons in anesthetized rats. Extracellular recordings were coupled to juxtacellular injections of neurobiotin or biotinylated dextran amine to morphologically differentiate interneurons from pyramidal cells. In all cases, the action potentials of labeled interneurons were of shorter duration ( 0.70 ms). Single pulse stimulation of the hippocampal CA1/subiculum region induced an excitatory response in 70% of recorded interneurons in the prelimbic and medial-orbital areas of the PFC. In contrast to the one to two action potentials generated by pyramidal cells, an important group of interneurons fired a burst of action potentials in response to hippocampal stimulation. A large proportion of these excitatory responses was probably monosynaptic as their latency is consistent with the conduction time of the hippocampo-prefrontal pathway. In addition, when both a pyramidal cell and an interneuron were simultaneously recorded and both responded to stimulation, the interneuron consistently fired before the pyramidal cell. In conclusion, the hippocampus exerts a direct excitatory influence on PFC interneurons and is thus capable of feedforward inhibition of pyramidal cells. Hippocampal output is spatially and temporally focalized via this inhibitory process and consequently could facilitate the synchronization of a specific subset of PFC neurons with hippocampal activity.

Influence of the hippocampus on interneurons of the rat prefrontal cortex.

In order to determine the electrophysiological properties of prefrontal cortex pyramidal neurons in vivo, intracellular recordings coupled with neurobiotin injection were performed in anesthetized rats. Three main classes of pyramidal cells were distinguished according to both their firing patterns in response to depolarizing current pulses and the characteristics of their action potentials: regular spiking (RS, n = 71); intrinsic (inactivating) bursting (IB, n = 8); and non-inactivating bursting (NIB, n = 26) cells. RS cells were further subdivided into slow-adapting and fast-adapting types, according to their firing frequency adaptation. IB and fast-adapting RS cells could exhibit different firing patterns depending on the intensity of the depolarizing current. In response to successive depolarizing pulses of a given intensity, NIB and some RS cells showed variations in their firing patterns, probably due to the impact of local synaptic activity. All the labeled neurons were pyramidal cells with an apical dendrite that formed a terminal tuft in layer I. As compared to RS cells, NIB cells had a smaller somatic size and their apical dendritic tuft was less extensive, while IB cells presented a larger somatic size, thicker dendrites and a wider extent of their basal and apical dendritic arborization. In conclusion, we found in the rat prefrontal cortex, in vivo, different electrophysiological classes of pyramidal cells whose output firing patterns depend on interactions between their intrinsic properties and the ongoing synaptic activity.

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Electrophysiological Properties of Pyramidal Neurons in the Rat Prefrontal Cortex: An In Vivo Intracellular Recording Study

The hippocampus and prefrontal cortex are two structures implicated in learning and memory and are related through a direct excitatory pathway. The characteristics of the synaptic influence of the hippocampus on pyramidal cells of the prefrontal cortex were determined using intracellular recordings in anesthetized rats. Single-pulse stimulation of the hippocampus induced an early EPSP of fixed latency in most of the recorded pyramidal cells (n = 106/116) thereby demonstrating a monosynaptic connection between hippocampal neurons and pyramidal cells of the prefrontal cortex. Furthermore, the EPSP was followed by a prolonged IPSP and suggests a simultaneous engagement of pyramidal and nonpyramidal neurons that may ultimately constrain the spread of excitation in response to hippocampal input. Paired-pulse stimulation induced short-term modifications in the synaptic responses and this short-term plasticity may contribute to the temporal filtering of information. Finally, tetanic stimulation of the hippocampus produced long-term potentiation of the monosynaptic EPSP with a concomitant potentiation of the IPSP, indicating that the hippocampo-prefrontal network can participate in the formation and consolidation of memories. In conclusion, the characteristics of the synaptic transmission in the hippocampo-prefrontal cortex pathway further supports the existence of a cooperative relationship between two structures known to be involved in higher cognitive processes.

Eric Dégenètais

Papers

Hippocampo-prefrontal cortex pathway: anatomical and electrophysiological characteristics.

Influence of the hippocampus on interneurons of the rat prefrontal cortex.

Electrophysiological Properties of Pyramidal Neurons in the Rat Prefrontal Cortex: An In Vivo Intracellular Recording Study

Synaptic Influence of Hippocampus on Pyramidal Cells of the Rat Prefrontal Cortex: An In Vivo Intracellular Recording Study