The hippocampus is assumed to retrieve memory by reinstating patterns of cortical activity that were observed during learning. To test this idea, we monitored the activity of individual cortical neurons while simultaneously inactivating the hippocampus. Neurons that were active during context fear conditioning were tagged with the long-lasting fluorescent protein H2B-GFP and the light-activated proton pump ArchT. These proteins allowed us to identify encoding neurons several days after learning and silence them with laser stimulation. When tagged CA1 cells were silenced, we found that memory retrieval was impaired and representations in the cortex (entorhinal, retrosplenial, perirhinal) and the amygdala could not be reactivated. Importantly, hippocampal inactivation did not alter the total amount of activity in most brain regions. Instead, it selectively prevented neurons that were active during learning from being reactivated during retrieval. These data provide functional evidence that the hippocampus reactivates specific memory representations during retrieval.

Interval-counting neurons (ICNs) respond after a threshold number of sound pulses have occurred with specific intervals; a single aberrant interval can reset the counting process. Female gray treefrogs, Hyla chrysoscelis and H. versicolor, discriminate against synthetic 'calls' possessing a single interpulse interval 2-3 three times the optimal value, suggesting that ICNs are important for call recognition. The calls of H. versicolor consist of pulses that are longer in duration, rise more slowly in amplitude and are repeated at a slower rate than those of H. chrysoscelis. Results of recordings from midbrain auditory neurons in these species include: (1) ICNs were found in both species and their temporal selectivity appeared to result from interplay between excitation and inhibition; (2) band-pass cells in H. versicolor were tuned to slower pulse rates than those in H. chrysoscelis; (3) ICNs that were selective for slow-rise pulse shape were found almost exclusively in H. versicolor, but fast-rise-selective neurons were found in both species, and (4) band-suppression ICNs in H. versicolor showed response minima at higher pulse rates than those in H. chrysoscelis. Selectivity of midbrain ICNs for pulse rise time and repetition rate thus correlate well with discriminatory abilities of these species that promote reproductive isolation.

Sound duration is important in acoustic communication, including speech recognition in humans. Although duration-selective auditory neurons have been found, the underlying mechanisms are unclear.To investigate these mechanisms we combined in vivo whole-cell patch recordings from midbrain neurons, extraction of excitatory and inhibitory conductances, and focal pharmacological manipulations. We show that selectivity for short-duration stimuli results from integration of short-latency, sustained inhibition with delayed, phasic excitation; active membrane properties appeared to amplify responses to effective stimuli. Blocking GABA A receptors attenuated stimulus-related inhibition, revealed suprathreshold excitation at all stimulus durations, and decreased short-pass selectivity without changing resting potentials. Blocking AMPA and NMDA receptors to attenuate excitation confirmed that inhibition tracks stimulus duration and revealed no evidence of postinhibitory rebound depolarization inherent to coincidence models of duration selectivity. These results strongly support an anticoincidence mechanism of short-pass selectivity, wherein inhibition and suprathreshold excitation show greatest temporal overlap for long duration stimuli.whole-cell | GABA | synaptic conductance | gabazine | inferior colliculus A principal goal in neuroscience is to understand the computational mechanisms that underlie selectivity for particular types of information. Sensory neurons have been identified that show selectivity for biologically relevant stimulus features; however, the underlying mechanisms are, in most cases, poorly understood. A notable exception involves mechanisms of selectivity for sound duration, particularly in bat and anuran auditory systems (1-3). Duration-selective neurons were first found in the midbrain torus semicircularis of anurans (4, 5), homolog of the mammalian inferior colliculus (IC) and referred to here as the IC an . In anurans and many mammalian species, midbrain neurons have been identified that show short-pass, band-pass, or long-pass duration selectivity (3, 6-11). These neurons code for temporal properties of acoustic signals that are important in communication and echolocation. Processing sound duration is also critical for human speech communication, and deficiencies in the neural processing of this and other temporal information feature prominently in disorders of speech recognition (12, 13). Hence, understanding the mechanisms of duration selectivity is of considerable importance.Several models of duration selectivity have been proposed. The first model, derived from extracellular recordings in the anuran IC (4), incorporates delayed, onset excitation and shortlatency offset excitation that coincide for the optimal stimulus duration (Fig. 1A). Subsequent extracellular recordings from IC neurons in bats showed that blocking receptors of inhibitory neurotransmitters eliminated, or greatly attenuated, duration selectivity (14-16). Further, the temporal pattern of discharges shifted from offset to onse...

Visual landmarks can anchor an animal’s internal sense of orientation to the external world. The rodent postrhinal cortex (POR) may facilitate this processing. Here, we demonstrate that, in contrast to classic head direction (HD) cells, which have a single preferred orientation, POR HD cells develop a second preferred orientation when an established landmark cue is duplicated along another environmental wall. We therefore refer to these cells as landmark-modulated–HD (LM-HD) cells. LM-HD cells discriminate between landmarks in familiar and novel locations, discriminate between visually disparate landmarks, and continue to respond to the previous location of a familiar landmark following its removal. Rats initially exposed to different stable landmark configurations show LM-HD tuning that may reflect the integration of visual landmark information into an allocentric HD signal. These results provide insight into how visual landmarks are integrated into a framework that supports the neural encoding of landmark-based orientation.

The hippocampus can be divided into distinct segments that make unique contributions to learning and memory. The dorsal segment supports cognitive processes like spatial learning and navigation while the ventral hippocampus regulates emotional behaviors related to fear, anxiety and reward. In the current study, we determined how pyramidal cells in ventral CA1 respond to spatial cues and aversive stimulation during a context fear conditioning task. We also examined the effects of high and low frequency stimulation of these neurons on defensive behavior. Similar to previous work in the dorsal hippocampus, we found that cells in ventral CA1 expressed high-levels of c-Fos in response to a novel spatial environment. Surprisingly, however, the number of activated neurons did not increase when the environment was paired with footshock. This was true even in the subpopulation of ventral CA1 pyramidal cells that send direct projections to the amygdala. When these cells were stimulated at high-frequencies (20 Hz) we observed feedforward inhibition of basal amygdala neurons and impaired expression of context fear. In contrast, low-frequency stimulation (4 Hz) did not inhibit principal cells in the basal amygdala and produced an increase in fear generalization. Similar results have been reported in dorsal CA1. Therefore, despite clear differences between the dorsal and ventral hippocampus, CA1 neurons in each segment appear to make similar contributions to context fear conditioning.

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In recently diverged gray treefrogs (Hyla chrysoscelis and H. versicolor), advertisement calls that differ primarily in pulse shape and pulse rate act as an important premating isolation mechanism. Temporally selective neurons in the anuran inferior colliculus may contribute to selective behavioral responses to these calls. Here we present in vivo extracellular and whole-cell recordings from long-interval-selective neurons (LINs) made during presentation of pulses that varied in shape and rate. Whole-cell recordings revealed that interplay between excitation and inhibition shapes long-interval selectivity. LINs in H. versicolor showed greater selectivity for slow-rise pulses, consistent with the slow-rise pulse characteristics of their calls. The steepness of pulse-rate tuning functions, but not the distributions of best pulse rates, differed between the species in a manner that depended on whether pulses had slow or fast-rise shape. When tested with stimuli representing the temporal structure of the advertisement calls of H. chrysoscelis or H. versicolor, approximately 27 % of LINs in H. versicolor responded exclusively to the latter stimulus type. The LINs of H. chrysoscelis were less selective. Encounter calls, which are produced at similar pulse rates in both species (≈5 pulses/s), are likely to be effective stimuli for the LINs of both species.

Whole-cell patch neurophysiology and pharmacological manipulations have provided unprecedented insight into the functions of central neurons, but their combined use has been largely restricted to in vitro preparations. We describe a method for performing whole-cell patch recording and focal application of pharmacological agents in vivo. A key feature of this technique involves iontophoresis of glutamate to establish proximity of drug and recording pipettes. We show data from iontophoresis of glutamate during extracellular and whole-cell recordings made in vivo from auditory neurons in the midbrain of the leopard frog, Rana pipiens, and the effects of blocking GABAA receptors while making a whole-cell recording. This methodology should accelerate our understanding of the roles of particular neurotransmitter systems in normal and pathological conditions, and facilitate investigation of the in vivo effects of drugs and the mechanisms underlying computations.